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Senescence of Natural/Innate Resistance to Infection

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Aging, Immunity, and Infection

Part of the book series: Infectious Disease ((ID))

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Abstract

It has been realized for decades that in humans and higher vertebrates there are, in addition to the adaptive immune system, accessory mechanisms and systems that contribute to overall immune defense against infectious organisms. They have been grouped under the heading “natural” or “innate” immunity. They include the reticuloendothelial system comprising “fixed” and “mobile” (circulating) monocytes (Mo’s) and macrophages (MPs), polymorphonuclear (PMN) cells (especially neutrophils and eosinophils that can discharge antimicrobial peptides such as defensins), natural killer (NK) and other “naturally cytotoxic” (NC) cells, and the complement (C) system; all of which have been preserved and handed down during the evolution of higher vertebrates from primitive vertebrates and invertebrates.

If an experiment does not hold out the possibility of causing one to revise one’s views, it is hard to see why it should be done at all.

—Peter Medawar, Advice to a Young Scientist

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References

  1. Janeway CA Jr. The immune system evolved to discriminate infectious nonself from noninfectious self. Immunol Today 1992; 13: 11–16.

    CAS  PubMed  Google Scholar 

  2. Hoffmann JA, Kafatos FC, Janeway CA Jr., Ezekowitz RAB. Phylogenetic perspectives in innate immunity. Science 1999; 284: 1313–1318.

    CAS  PubMed  Google Scholar 

  3. Epstein J, Eichbaum Q, Sheriff S, Ezekowitz RAB. The collectins in innate immunity. Curr Opin Immunol 1996; 8: 29–35.

    CAS  PubMed  Google Scholar 

  4. Pearson AM. Scavenger receptors in innate immunity. Curr Opin Immunol 1996; 8: 20–28.

    CAS  PubMed  Google Scholar 

  5. Weis WI, Drickamer K, Hendrickson WA. Structure of a C-type mannose-binding protein complexed with an oligosaccharide. Nature 1992; 360: 127–134.

    CAS  PubMed  Google Scholar 

  6. Weis WI, Taylor ME, Drickamer K. The C-type lectin superfamily in the immune system. Immunol Rev 1998; 163: 19–34.

    CAS  PubMed  Google Scholar 

  7. Gadjeva M, Thiel S, Jensenius JC. The mannan-binding-lectin pathway of the innate immune response. Curr Opin Immunol 2001; 13: 774–778.

    Google Scholar 

  8. Hoppe HJ, Barlow PN, Reid KB. A parallel three stranded alpha helical bundle at the nucleation site of collagen triple-helix formation. FEBS Lett 1994; 344: 191–195.

    CAS  PubMed  Google Scholar 

  9. Sheriff S, Chang CY, Ezekowitz RAB. Human mannose-binding protein carbohydrate recognition domain trimerizes through a triple a-helical coiled coil. Nature Struct Biol 1994; 1: 789–794.

    CAS  PubMed  Google Scholar 

  10. Reid KB, Turner MW. Mammalian lectins in activation and clearance mechanisms involving the complement system. Springer Semin Immunopathol 1994; 15: 307–336.

    CAS  PubMed  Google Scholar 

  11. Malhotra R, Lu J, Holmskov U, Sim RB. Collectins, collectin receptors and the lectin pathway of complement activation. Clin Exp Immunol 1994; 97 (S2): 4–9.

    CAS  PubMed Central  PubMed  Google Scholar 

  12. Ikeda K, Sannoh T, Kawasaki N, Kawasaki T, et al. Serum lectin with known structure activates complement through the classical pathway. J Biol Chem 1987; 262: 7451–7454.

    CAS  PubMed  Google Scholar 

  13. Kuhlman M, Joiner K, Ezekowitz RA. The human mannose-binding protein functions as an opsonin. J Exp Med 1989; 169: 1733–1745.

    CAS  PubMed  Google Scholar 

  14. Pikaar JC, Voorhout WF, Van Golde LM, et al. Opsonic activities of surfactant proteins A and D in phagocytosis of gram-negative bacteria by alveolar macrophages. J Infect Dis 1995; 172: 481–489.

    CAS  PubMed  Google Scholar 

  15. Taylor ME, Bezouska K, Drickamer K. Contribution to ligand binding by multiple carbohydrate-recognition domains in the macrophage mannose receptor. J Biol Chem 1992; 267: 1719–1726.

    CAS  PubMed  Google Scholar 

  16. Martinez-Pomares L, Gordon S. The mannose receptor and its role in antigen presentation. The Immunologist 1999; 7: 119–123.

    CAS  Google Scholar 

  17. Anderson KV, Jurgens G, Nusslein-Volhard C. Establishment of dorsal-ventral polarity in the Drosophila embryo: Genetic studies on the role of the Toll gene product. Cell 1985; 42: 779–789.

    CAS  PubMed  Google Scholar 

  18. Anderson KV. Pinning down positional information: Dorsal-ventral polarity in the Drosophila embryo. Cell 1998; 95: 439–442.

    CAS  PubMed  Google Scholar 

  19. Belvin MP, Anderson KV. A conserved signaling pathway: The Drosophila Toll-Dorsal pathway. Annu Rev Cell Dev Biol 1996; 12: 3343–3416.

    Google Scholar 

  20. Lemaitre B, Meister M, Govind S, et al. Functional analysis and regulation of nuclear import of Dorsal during the immune response in Drosophila. EMBO J 1995; 14: 536–545.

    CAS  PubMed  Google Scholar 

  21. Lemaitre B, Nicolas E, Michaut L, et al. The dorsoventral regulatory gene cassette spaetzle/Toll/cactus controls the patent antifungal response in Drosophila adults. Cell 1996; 86: 973–983.

    CAS  PubMed  Google Scholar 

  22. Lemaitre B, Reichhart JM, Hoffmann JA. Drosophila host defense: Differential induction of antimicrobial peptide genes after infection by various classes of microorganisms. Proc Natl Acad Sci USA 1997; 94: 14, 614–14, 619.

    Google Scholar 

  23. Medzhitov R, Preston-Hurlburt P, Janeway Jr, CA. A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 1997; 338: 394–397.

    Google Scholar 

  24. Rock FL, Hardiman G, Timans JC, et al. A family of human receptors structurally related to Drosophila Toll Proc Natl Acad Sci USA 1998; 95: 588–593.

    CAS  Google Scholar 

  25. Medzhitov R, Janeway CA Jr. Innate immune recognition: Mechanisms and pathways. Immunol Rev 2000; 173; 89–97.

    CAS  PubMed  Google Scholar 

  26. Brightbill HD, Libraty DH, Krutzik SR, et al. Host defense mechanisms triggered by microbial lipoproteins through toll-like receptors. Science 1999; 285: 732–736.

    CAS  PubMed  Google Scholar 

  27. Takeuchi O, Kaufmann A, Grote K, et al. Preferentially the R-stereoisomer of the mycoplasmal lipopeptide macrophage-activating lipopeptide-2 activates immune cells through a toll-like receptor 2- and My 88-dependent signaling pathway. J Immunol 2000; 164: 554–557.

    CAS  PubMed  Google Scholar 

  28. Hirschfeld M, Kirschning CJ, Schwandner R, et al. Inflammatory signaling by Borrelia burgdorferi lipoproteins is mediated by toll-like receptor 2. J Immunol 1999; 163: 2382–2386.

    CAS  PubMed  Google Scholar 

  29. Flo TH, Halaas O, Lien E, et al. Human toll-like receptor 2 mediates monocyte activation by Listeria monocytogenes, but not by group B streptococci or lipopolysaccharide. J Immunol 2000; 164: 2064–2069.

    CAS  PubMed  Google Scholar 

  30. Yoshimura A, Lien E, Ingalls RR, et al. Recognition of Gram-positive bacterial cell wall components by the innate immune system occurs via Toll-like receptor 2. J Immunol 1999; 163: 1–5.

    CAS  PubMed  Google Scholar 

  31. Poltorak A, Xiaolong H, Smirnova I, et al. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: Mutations in Tlr 4 gene. Science 1998; 282: 2085–2088.

    CAS  PubMed  Google Scholar 

  32. Qureshi ST, Lariviere L, Leveque G, et al. Endotoxin-tolerant mice have mutations in toll-like receptor 4 (Tlr 4). J Exp Med 1999; 189: 615–625.

    CAS  PubMed Central  PubMed  Google Scholar 

  33. Hoshino K, Takeuchi O, Kawai T, et al. Cutting edge: Toll-like receptor 4 (TLR 4)-deficient mice are hyporesponsive to lipopolysaccharide: Evidence for TLR 4 as the 1ps gene product. J Immunol 1999; 162: 3749–3752.

    CAS  PubMed  Google Scholar 

  34. Perera P-Y, Mayadas TN, Takeuchi O, et al. CD 1 l b/CD 18 acts in concert with CD14 and toll-like receptor (TLR) 4 to elicit full lipopolysaccharide and taxolinducible gene expression. J Immunol 2001; 166: 574–581.

    CAS  PubMed  Google Scholar 

  35. Kirschning CJ, Wesche H, Ayres TM, Rothe M. Human Toll-like receptor 2 confers responsiveness to bacterial lipopolysaccharide. J Exp Med 1998; 188; 2091–2096.

    CAS  PubMed Central  PubMed  Google Scholar 

  36. Yang R-B, Mark MR, Gurney AL, Godowski PJ. Signaling events induced by lipopolysaccharide-activated toll-like receptor 2. J Immunol 1999; 163: 639–643.

    CAS  PubMed  Google Scholar 

  37. Hirschfeld M, Ya Y, Weis JH, et al. Cutting edge: Repurification of lipopolysaccharide eliminates signaling through both human and murine Toll-like receptor 2. J Immunol 2000; 165: 618–622.

    CAS  PubMed  Google Scholar 

  38. Sato S, Nomura F, Kawai T, et al. Synergy and cross-tolerance between Toll-like receptor (TLR) 2- and TLR 4-mediated signaling pathways. J Immunol 2000; 165: 7096–7101.

    CAS  PubMed  Google Scholar 

  39. Wright SD, Ramos RA, Tobias PS, et al. CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding proteins. Science 1990; 249: 1431–1434.

    CAS  PubMed  Google Scholar 

  40. Haziot A, Chen S, Ferrero E, et al. The monocyte differentiation antigen, CD 14, is anchored to the cell membrane by a phosphatidylinositol linkage. J Immunol 1998; 141: 547–551.

    Google Scholar 

  41. Underhill DM, Ozinsky A, Hajjar AM, et al. The Toll-like receptor 2 is recruited to macrophage phagosomes and discriminates between pathogens. Nature 1999; 401: 811–815.

    CAS  PubMed  Google Scholar 

  42. Brightbill HD, Modlin RL. Toll-like receptors: Molecular mechanisms of the mammalian immune response. Immunology 2000; 101: 1–10.

    CAS  PubMed  Google Scholar 

  43. Hughes DA, Fraser IP, Gordon S. Murine macrophage scavenger receptor: In vivo expression and function as a receptor for macrophage adhesion in lymphoid and non-lymphoid organs. Eur J Immunol 1995; 25: 466–473.

    CAS  PubMed  Google Scholar 

  44. Elomaa O, Kangas M, Sahlberg C, et al. Cloning of a novel bacteria-binding receptor structurally related to scavenger receptors and expressed in subset of macrophages. Cell 1995; 80: 603–609.

    CAS  PubMed  Google Scholar 

  45. Arai H, Kita T, Yokode M, et al. Multiple receptors for modified low density lipoproteins in mouse peritoneal macrophages: Different uptake mechanisms for acetylated and oxidized low density lipoproteins. Biochem Biophys Res Communs 1989; 159: 1375–1382.

    CAS  Google Scholar 

  46. Thai SF, Lewis JG, Williams RB, et al. Effects of oxidized LDL on mononuclear phagocytosis: Inhibition of induction of four inflammatory cytokine gene RNAs, release of NO and cytolysis of tumor cells. J Leukoc Biol 1995; 57: 427–33.

    CAS  PubMed  Google Scholar 

  47. Biwa T, Hakamata H, Sakai M, et al. Induction of murine macrophage growth by oxidized low density lipoprotein is mediated by granulocyte macrophage colony-stimulating factor. J Biol Chem 1998; 273: 28, 305–28, 313.

    Google Scholar 

  48. Gillotte KL, Horkko S, Witztum JL, Steinberg D. Oxidized phospholipids, linked to apolipoprotein B of oxidized LDL, are ligands for macrophage scavenger receptors. J Lipid Res 2000; 41: 824–833.

    CAS  PubMed  Google Scholar 

  49. Tontonoz P, Nagy L, Alvarez JG, et al. PPAR gamma promotes monocyte/macrophage differentiation and uptake of oxidized LDL. Cell 1998; 93: 241–252.

    CAS  PubMed  Google Scholar 

  50. Singh N, Bhatia S, Abraham R, et al. Modulation of T cell cytokine profiles and peptide-MHC complex availability in vivo by delivery to scavenger receptors via antigen maleylation. J Immunol 1998; 160: 4869–4880.

    CAS  PubMed  Google Scholar 

  51. Bansal P, Mukherjee P, Basu SK, et al. MHC class I-restricted presentation of maleylated protein binding to scavenger receptors. J Immunol 1999; 162: 4430–4437.

    CAS  PubMed  Google Scholar 

  52. Sutterwala FS, Noel GJ, Clynes R, Mosser DM. Selective suppression of interleukin-12 induction after macrophage receptor ligand. J Exp Med 1997; 185: 1977–1985.

    CAS  PubMed Central  PubMed  Google Scholar 

  53. Gough PJ, Gordon S. The role of scavenger receptors in the innate immune system. Microbes Infect 2000; 2: 305–311.

    CAS  PubMed  Google Scholar 

  54. Thomas CA, Li Y, Kodama T, et al. Protection from lethal gram-positive infection by macrophage scavenger-dependent phagocytosis. J Exp Med 2000; 191: 147–156.

    CAS  PubMed Central  PubMed  Google Scholar 

  55. Peiser L, Gough PJ, Kodoma T, Gordon S. Macrophage class A scavenger receptor-mediated phagocytosis of Escherichia coli: Role of cell heterogeneity, microbial strain, and culture conditions in vitro. Infect Immun 2000; 68: 1953–1963.

    CAS  PubMed Central  PubMed  Google Scholar 

  56. Ito S, Naito M, Kobayashi Y, et al. Roles of a macrophage receptor with collagenous structure (MARCO) in host defense and heterogeneity of splenic marginal zone macrophages. Arch Histol Cytol 1999; 62; 83–95.

    CAS  PubMed  Google Scholar 

  57. Van der Laan LJ, Dopp EA, Haworth R, et al. Regulation and functional involvement of macrophage scavenger receptor MARCO in clearance of bacteria in vivo. J Immunol 1999; 162: 939–947.

    PubMed  Google Scholar 

  58. Acton S, Rigotti A, Landschulz KT, et al. Identification of scavenger receptor SR-BI as a high density lipoprotein receptor. Science 1996; 271: 518–520.

    CAS  PubMed  Google Scholar 

  59. Ibrahim MAA, Chaim BM, Katz DR. The injured cell: The role of the dendritic cell system as a sentinel receptor pathway. Immunol Today 1995; 16: 181–186.

    CAS  PubMed  Google Scholar 

  60. Savill J, Hogg N, Ren Y, Haslett C. Thrombospondin cooperates with CD 36 and the vitronectin receptor in macrophage recognition of neutrophils undergoing apoptosis. J Clin Invest 1992; 90: 1513–1522.

    CAS  PubMed Central  PubMed  Google Scholar 

  61. Terpstra V, van Berkel TJ. Scavenger receptors on liver Kupffer cells mediate the in vivo uptake of oxidatively damaged red blood cells in mice. Blood 2000; 95: 2157–2163.

    CAS  PubMed  Google Scholar 

  62. Lodish H, Baltimore D, Berk A, Zipursky SL, Matsudaira P, Darnell J. Molelcular Cell Biology, 3rd ed. New York: Scientific American Books, 1995: 837–839.

    Google Scholar 

  63. Styles JA, Kelly M, Pritchard NR, Elcombe CR. A species comparison of acute hyperplasia induced by the peroxisome proliferator methylclofenapate: Involvement of the binucleated hepatocyte. Carcinogenesis 1988; 9: 1647–1655.

    CAS  Google Scholar 

  64. Lock EA, Mitchell AM, Elcombe CR. Biochemical mechanisms of induction of hepatic peroxisome proliferation. Annu Rev Pharmacol Toxicol 1989; 29: 145–163.

    CAS  PubMed  Google Scholar 

  65. Kliewer SA, Lenhard JM, Willson TM, et al. A prostaglandin J2 metabolite binds peroxisome proliferator-activated receptor y and promotes adipocyte differentiation. Cell 1995; 83: 813–819.

    CAS  PubMed  Google Scholar 

  66. Forman BM, Tontonoz P, Chen J, et al. 15-Deoxy-cD 12,14-prostaglandin J2 is a ligand for the adipocyte determination factor PPARy. Cell 1995; 83: 803–812.

    CAS  PubMed  Google Scholar 

  67. Ricote M, Huang JT, Welch JS, Glass CK. The peroxisome proliferator-activated receptor y (PPARy) as a regulator of monocyte/macrophage function. J Leukoc Biol 1999; 66: 733–739.

    CAS  PubMed  Google Scholar 

  68. Jiang C, Ting AT, Seed B. PPAR-gamma agonists inhibit production of monocyte inflammatory cytokines. Nature 1998; 391: 82–86.

    CAS  PubMed  Google Scholar 

  69. Thieringer R, Fenyk-Melody JE, Le Grand CB, et al. Activation of peroxisome proliferator-activated receptor y does not inhibit IL-6 or TNF-a responses of macrophages to lipopolysaccharide in vitro or in vivo. J Immunol 2000; 164: 1046–1054.

    CAS  PubMed  Google Scholar 

  70. Poynter ME, Daynes RA. Peroxisome proliferator-activated receptor a activation modulates cellular redox status, represses nuclear factor-KB signaling and reduces inflammatory cytokine production in aging. J Biol Chem 1998; 273; 32, 833–32, 841.

    Google Scholar 

  71. Poynter ME, Daynes RA. Age-associated alterations in splenic iNOS regulation: Influence of constitutively expressed IFNy and correction following supplementation with PPARa activators or vitamin E. Cell Immunol 1999; 195: 127–136.

    CAS  Google Scholar 

  72. Berlett BS, Stadtman ER. Protein oxidation in aging, disease, and oxidative stress. J Biol Chem 1997; 272: 20, 313–20, 316.

    Google Scholar 

  73. Beckman KB, Ames BN. The free radical theory of aging matures. Physiol Rev 1998; 78: 547–581.

    CAS  PubMed  Google Scholar 

  74. Sohal RS, Orr WC. Role of oxidative stress in senescence. Aging (Milano) 1998; 10: 149–151.

    CAS  Google Scholar 

  75. Rabinovitch M. Professional and non-professional phagocytes: An introduction. Trends Cell Biol 1995; 5: 85–87.

    Google Scholar 

  76. Wright SD, Craigmyle LS, Silverstein SC. Fibronectin and serum amyloid P component stimulate C3b-and C3bi-mediated phagocytosis in cultured human monocytes. J Exp Med 1983; 158: 1338–1343.

    CAS  PubMed  Google Scholar 

  77. Ravetch JV. Fc receptors: Rubor redux. Cell 1994; 78: 553–560.

    CAS  Google Scholar 

  78. Aderem A, Underhill DM. Mechanisms of phagocytosis in macrophages. Annu Rev Immunol 1999; 17: 593–623.

    CAS  PubMed  Google Scholar 

  79. Griffin FM, Griffin JA, Silverstein SC. Studies on the mechanism of phagocytosis. II. The interaction of macrophages with anti-immunoglobulin IgG-coated bone marrow derived lymphocytes. J Exp Med 1976; 144: 788–809.

    PubMed  Google Scholar 

  80. Swanson JA, Baer SC. Phagocytosis by zippers and triggers. Trends Cell Biol 1995; 5: 89–93.

    CAS  PubMed  Google Scholar 

  81. Berton G, Gordon S. Modulation of macrophage mannosyl-specific receptors by cultivation on immobilized zymosan. Effects on superoxide-anion release and phagocytosis. Immunology 1983; 49: 705–713.

    CAS  PubMed  Google Scholar 

  82. Rouzer CA, Scott WA, Hamill AL, Cohn ZA. Synthesis of leukotriene C and other arachidonic acid metabolites by mouse pulmonary macrophages. J. Exp. Med. 1982; 155: 720–728.

    CAS  PubMed  Google Scholar 

  83. Aderem AA, Wright SD, Silverstein SC, Cohn ZA. Ligated complement receptors do not activate the arachidonic acid cascade in resident peritoneal macrophages. J Exp Med 1985; 161: 617–622.

    CAS  PubMed  Google Scholar 

  84. Wright SD, Silverstein SC. Receptors for C3b and C3bi promote phagocytosis but not the release of toxic oxygen from human phagocytes. J Exp Med 1983; 158: 2016–2023.

    CAS  PubMed  Google Scholar 

  85. Greenberg S. Signal transduction of phagocytosis. Trends Cell Biol 1995; 5: 93–99.

    CAS  PubMed  Google Scholar 

  86. Greenberg S. Modular components of phagocytosis. J Leukoc Biol 1999; 66: 712–717.

    CAS  PubMed  Google Scholar 

  87. Beron W, Alvarez-Dominguez C, Mayorga L, Stahl PD. Membrane trafficking along the phagocytic pathway. Trends Cell Biol 1995; 5: 100–104.

    CAS  PubMed  Google Scholar 

  88. Bogdan C, Rollinghoff M, Diefenbach A. Reactive oxygen and reactive nitrogen intermediates in innate and specific immunity. Curr Opin Immunol 2000; 12: 64–76.

    CAS  PubMed  Google Scholar 

  89. Bokoch GM. Regulation of the phagocyte respiratory burst by small GTP-binding proteins. Trends Cell Biol 1995; 5: 109–113.

    CAS  PubMed  Google Scholar 

  90. Heinecke JW. The respiratory burst of neutrophils: oxidative pathways for the initiation of tissue damage at site of inflammation. In: Gabrilovich DI, ed. The Neutrophils: New Outlook for Old Cells. London: Imperial College Press, 1999: 31–57.

    Google Scholar 

  91. Bergendi L, Benes L, Durackova Z, Ferencik M. Chemistry, physiology and pathology of free radicals. Life Sciences 1999; 65: 1865–1874.

    CAS  PubMed  Google Scholar 

  92. Bogdan C. Nitric oxide and the regulation of gene expression. Trends Cell Biol 2001; 11: 66–75.

    CAS  PubMed  Google Scholar 

  93. Mac Micking J, Xie QW, Nathan C. Nitric oxide and macrophage function. Annu Rev Immunol 1997; 15: 323–350.

    CAS  PubMed  Google Scholar 

  94. Connelly L, Palacios-Callender M, Ameixa C, et al. Biphasic regulation of NFiB activity underlies the pro-and anti-inflammatory actions of nitric oxide. J Immunol 2001; 166: 3873–3881.

    CAS  PubMed  Google Scholar 

  95. Janssen-Heininger YMW, Poynter ME, Bauerle PA. Recent advances towards understanding redox mechanisms in the activation of nuclear factor KB. Free Radic Biol Med 2000; 28: 1317–1327.

    CAS  PubMed  Google Scholar 

  96. Umansky V, Hehner SP, Dumont A, et al. Co-stimulatory effect of nitric oxide on endothelial NF-kappa B implies a physiological self-amplifying mechanism. Eur J Immunol 1998; 28: 2276–2282.

    CAS  PubMed  Google Scholar 

  97. Katsuyama K, Shichiri M, Marumo F, Hirata Y. NO inhibits cytokine-induced iNOS expression and NF-kappa B activation by interfering with phosphorylation and degradation of I kappa B-alpha. Arterioscler Thromb Vasc Biol 1998; 18: 1796–1802.

    CAS  PubMed  Google Scholar 

  98. Lowenstein CJ, Alley EW, Raval P, et al. Macrophage nitric oxide synthase gene: Two upstream regions mediate induction by interferon yand lipopolyssaccharide. Proc Natl Acad Sci USA 1993; 90: 9730–9734.

    CAS  PubMed  Google Scholar 

  99. Talor BS, de Vera ME, Ganster RW, et al. Multiple NFKB enhancer elements regulate cytokine induction of the human inducible nitric oxide synthase gene. J Biol Chem 1998; 273: 15, 148–15, 156.

    Google Scholar 

  100. Perkins DJ, Kniss DA. Blockade of nitric oxide formation down-regulates cyclooxygenase-2 and decreases PGE2 biosynthesis in macrophages. J Leukoc Biol 1999; 65: 792–797.

    CAS  PubMed  Google Scholar 

  101. Habib A, Bernard C, Lebret M, et al. Regulation of the expression of cyclooxygenase-2 by nitric oxide in rat peritoneal macrophages. J Immunol 1997; 158: 3845–3849.

    CAS  PubMed  Google Scholar 

  102. Wang S, Wang W, Wesley RA, Danner RL. A Sp1 binding site of the tumor necrosis factor a promoter functions as a nitric oxide response element. J Biol Chem 1999; 274: 33, 190–33, 193.

    Google Scholar 

  103. Schroeder RA, Cai C, Kuo PC. Endotoxin-mediated nitric oxide synthesis inhibits IL-1 13 gene transcription in ANA-1 murine macrophages. Am J Physiol 1999; 277: 523–0527.

    Google Scholar 

  104. Thomassen MJ, Buhrow LT, Connors MJ, et al. Nitric oxide inhibits inflammatory cytokine production by human alveolar macrophages. Am J Respir Cell Mol Biol 1997; 17: 729–737.

    Google Scholar 

  105. Persoons JH, Schornagel K, Tilders FF, et al. Alveolar macrophages autoregulate IL-1 and IL-6 production by endogenous nitric oxide. Am J Respir Cell Mol Biol 1996; 14: 272–278.

    CAS  PubMed  Google Scholar 

  106. Tetsuka T, Daphna-Iken D, Miller BW, et al. Nitric oxide amplifies interleukin 1-induced cyclooxygenase-2 expression in rat mesangial cells. J Clin Invest 1996; 97: 2051–2057.

    CAS  PubMed Central  PubMed  Google Scholar 

  107. Karin M, Ben-Neriah Y. Phosphorylation meets ubiquitination: The control of NF-KB activity. Annu Rev Immunol 2000; 18: 621–663.

    CAS  PubMed  Google Scholar 

  108. Peng HB, Libby P, Liao JK. Induction and stabilization of IiBa by nitric oxide mediates inhibition of NFxB. J Biol Chem 1995; 270: 14214–14219.

    CAS  PubMed  Google Scholar 

  109. De la Torre A, Schroeder RA, Punzalan C, Kuo PC. Endotoxin-mediated Snitrosylation of p50 alters NF-KB-dependent gene transcription in ANA-1 murine macrophages. J Immunol 1999; 162: 4101–4108.

    Google Scholar 

  110. Lander HM, Hajjar DP, Hempstead BL, et al. A molecular redox switch on p2lras: Structural basis for the nitric oxide-p21ras interaction. J Biol Chem 1997; 272: 4323–4326.

    CAS  PubMed  Google Scholar 

  111. Yun HY, Gonzalez-Zulueta M, Dawson VL, Dawson TM. Nitric oxide mediates N-methyl-D-aspartate receptor-induced activation of p2 Vas. Proc Natl Acad Sci USA 1998; 95: 5773–5778.

    CAS  PubMed  Google Scholar 

  112. Brady TC, Chang LY, Day BJ, Crapo JD. Extracellular superoxide dismutase is upregulated with inducible nitric oxide synthase after NF-KB activation. Am J Physiol 1997; 273: 1002–1006.

    Google Scholar 

  113. Mullins DW, Burger CJ, Elgert KD. Paclitaxel enhances macrophages IL-12 production in tumor-bearing hosts through nitric oxide. J Immunol 1999; 162: 6811–6818.

    CAS  PubMed  Google Scholar 

  114. Diefenbach A, Schindler H, Donhauser N, et al. Type 1 interferon (IFN-a/13) and type 2 nitric oxide synthase regulate the innate immune response to a protozoan parasite. Immunity 1998; 8: 77–87.

    CAS  PubMed  Google Scholar 

  115. Huang F-P, Niedbala W, Xiao-Qing W, et al. Nitric oxide regulates Thl cell development through the inhibition of IL-12 synthesis by macrophages. Eur J Immunol 1998; 28: 4062–4070.

    CAS  PubMed  Google Scholar 

  116. Sutterwala FS, Noel GJ, Clynes R, Mosser DM. Selective suppression of interleukin-12 induction after macrophage receptor ligation. J Exp Med 1997; 185: 1977–1985.

    CAS  PubMed Central  PubMed  Google Scholar 

  117. Wittmann M, Zwirner J, Larsson V-A, et al. C5a suppresses the production of IL-12 by IFN-y-primed and lipopolysaccharide-challenged human monocytes. J Immunol 1999; 162: 6763–6769.

    CAS  PubMed  Google Scholar 

  118. Wittman M, Larsson V-A, Schmidt P, et al. Suppression of interleukin-12 production by human monocytes after preincubation with lipopolysaccharide. Blood 1999; 94: 1717–1726.

    Google Scholar 

  119. Conboy IM, Manoli D, Mhaiskar V, Jones PP. Calcineurin and vacuolar-type H+-ATPase modulate macrophage effector functions. Proc Natl Acad Sci USA 1999; 96: 6324–6329.

    CAS  PubMed  Google Scholar 

  120. Pieters J. Evasion of host cell defense mechanisms by pathogenic bacteria. Curr Opin Immunol 2001; 13: 37–44.

    CAS  PubMed  Google Scholar 

  121. Kenny B, DeVinney R, Stein M, et al. Enteropathogenic E. coli (EPEC) transfers its receptor for intimate adherence into mammmalian cells. Cell 1997; 91: 511–520.

    CAS  PubMed  Google Scholar 

  122. Galan JE, Collmer A. Type III secretion machimes: Bacterial devices for protein delivery into host cells. Science 1999; 284: 1322–1328.

    CAS  PubMed  Google Scholar 

  123. Ochman H, Lawrence JG, Groisman EA. Lateral gene transfer and the nature of bacterial innovation. Nature 2000; 405: 299–304.

    CAS  PubMed  Google Scholar 

  124. Mengaud J, Ohayon H, Gounon P, et al. E-cadherin is the receptor for internalin, a surface protein required for entry of L. monocytogenes into epithelial cells. Cell 1996; 84: 923–932.

    CAS  PubMed  Google Scholar 

  125. Braun L, Ghebrehiwet B, Cossart P. GC1q-R/p32, a Clq-binding protein, is a receptor for the In1B invasion protein of Listeria monocytogenes. EMBO J 2000; 19: 1458–1466.

    CAS  PubMed  Google Scholar 

  126. Yamamoto K, Johnston RB Jr. Dissociation of phagocytosis from stimulation of the oxidative burst in macrophages. J Exp Med 1984; 159: 405–416.

    CAS  PubMed  Google Scholar 

  127. Caron E, Hall A. Identification of two distinct mechanisms of phagocytosis controlled by different Rho GTPases. Science 1998; 282: 1717–1721.

    CAS  PubMed  Google Scholar 

  128. Schorey JS, Carroll MC, Brown EJ. A macrophage invasion mechanism of pathogenic mycobacteria. Science 1997; 277: 1091–1093.

    CAS  PubMed  Google Scholar 

  129. Gatfield J, Pieters J. Essential role for cholesterol in entry of mycobacteria into macrophages. Science 2000; 288: 1647–1650.

    CAS  PubMed  Google Scholar 

  130. Goebel W, Kuhn M. Bacterial replication in the host cell cytosol. Curr Opin Microbiol 2000; 3: 49–53.

    CAS  PubMed  Google Scholar 

  131. Russell DG. Mycobacterium and Leishmania: Stowaways in the endosomal network. Trends Cell Biol 1995; 5: 125–128.

    Google Scholar 

  132. Sibley DL. Invasion of vertebrate cells by Toxoplasma gondii. Trends Cell Biol 1995; 5: 129–132.

    CAS  PubMed  Google Scholar 

  133. Andrews NW. Lysosome recruitment during host cell invasion by Trypanosoma cruzi. Trends Cell Biol 1995; 5: 133–137.

    CAS  PubMed  Google Scholar 

  134. Dominguez M, Torano A. Immune adherence-mediated opsonophagocytosis: The mechanisms of Leishmania infection. J Exp Med 1999; 189: 25–35.

    CAS  PubMed Central  PubMed  Google Scholar 

  135. Leenen PJM, de Bruijn MFTR, Voerman JSA, Campbell PA, van Ewijk W. Markers of mouse macrophage development detected by monoclonal antibodies. J Immunol Meth 1994; 174: 5–19.

    CAS  Google Scholar 

  136. Leenen PJM, Campbell PA. Heterogeneity of mononuclear phagocytes: An interpretive review. In: Horton MA, ed. Blood Cell Biochemistry: Vol. 5. Macrophages and Related Cells. New York: Plenum, 1993: 29–85.

    Google Scholar 

  137. Rutherford MS, Witsell A, Schook LB. Mechanisms generating functionally heterogeneous macrophages: Chaos revisited. J Leukoc Biol 1993; 53: 602–618.

    CAS  PubMed  Google Scholar 

  138. Davila DR, Edwards CKIII, Arkins S, et al. Interferon-y-induced priming for secretion of superoxide anion and tumor necrosis factor-a declines in macrophages from aged rats. FASEB J 1990; 4: 2906–2911.

    CAS  PubMed  Google Scholar 

  139. Ding A, Hwang S, Schwab R. Effect of aging on murine macrophages: Diminished response to IFNy for enhanced oxidative metabolism. J Immunol 1994; 153: 2146–2152.

    CAS  PubMed  Google Scholar 

  140. Fulop T Jr., Hauck M, Worum I, et al. Alterations of the FMLP-induced Cat+ efflux from human monocytes with aging. Immunol Lett 1987; 14: 283–286.

    CAS  PubMed  Google Scholar 

  141. Bruce IN, McNally JA, Rea IM, Bell AL. Age-related changes in non-receptor dependent generation of reactive oxygen species from phagocytes of healthy adults. Mech Ageing Dev 1997; 94: 135–144.

    CAS  PubMed  Google Scholar 

  142. Clark RA. The human neutrophil respiratory burst oxidase. J Inf Dis 1990; 161: 1140–1147.

    CAS  Google Scholar 

  143. Rosen GM, Pou S, Ramos CL, et al. Free radicals and phagocytic cells. FASEB J 1995; 9: 200–209.

    CAS  PubMed  Google Scholar 

  144. Alvarez E, Conde M, Machado A, et al. Decrease in free-radical production with age in rat peritoneal macrophages. Biochem J 1995; 312 (P2): 555–560.

    CAS  PubMed  Google Scholar 

  145. Lavie L, Weinreb O, Gershon D. Age-related alterations in superoxide anion generation in mouse peritoneal macrophages studied by repeated stimulations and heat shock treatment. J Cell Physiol 1992; 152: 382–388.

    CAS  PubMed  Google Scholar 

  146. Alvarzez E, Santa Maria C, Machado A. Respiratory burst reaction changes with age in rat peritoneal macrophages. Biochim Biophys Acta 1993; 1179: 247–252.

    Google Scholar 

  147. Cao D, Boxer LA, Petty HR. Deposition of reactive oxygen metabolites onto and within living tumor cells during neutrophil-mediated antibody-dependent cellular cytotoxicity. J Cell Physiol 1993; 156: 428–436.

    CAS  PubMed  Google Scholar 

  148. Amer ESJ, Holmgren A. Physiological functions of thioredoxin and thioredoxin reductase. Eur J Biochem 2000; 167: 6102–6109.

    Google Scholar 

  149. Powis G, Mustachich D, Coon A. The role of the redox protein thioredoxin in cell growth and cancer. Free Radical Biol Med 2000; 29: 312–322.

    CAS  Google Scholar 

  150. Chen L-C, Pace JL, Russell SW, Morrison DC. Altered regulation of inducible nitric oxide synthase expression in macrophages from senescent mice. Infect Immun 1996; 64: 4288–4298.

    CAS  PubMed Central  PubMed  Google Scholar 

  151. Chorinchath BB, Kong L-Y, Mao L, McCallum RE. Age-associated differences in TNF-a and nitric oxide production in endotoxic mice. J Immunol 1996; 156: 1525–1530.

    CAS  PubMed  Google Scholar 

  152. Wallace PK, Eisenstein TK, Meissler JJ Jr., Morahan PS. Decreases in macrophage mediated antitumor activity with aging. Mech Ageing Dev 1995; 77: 169–184.

    CAS  PubMed  Google Scholar 

  153. Sohal RS, Weindruch R. Oxidative stress, caloric restriction, and aging. Science 1996; 273: 59–63.

    CAS  PubMed Central  PubMed  Google Scholar 

  154. Beckman KB, Ames BN. The free radical theory of aging matures. Physiol Rev 1998; 78: 547–581.

    CAS  PubMed  Google Scholar 

  155. Salvioli S, Bonafe M, Capri M, et al. Mitochondria, aging and longevity-A new perspective. FEBS Lett 2001; 492: 9–13.

    CAS  PubMed  Google Scholar 

  156. Morel Y, Barouki R. Repression of gene expression by oxidative stress. Biochem J 1999; 342: 481–496.

    CAS  PubMed  Google Scholar 

  157. Allen RG, Tresini M. Oxidative stress and gene regulation. Free Radical Biol Med 2000; 28: 463–499.

    CAS  Google Scholar 

  158. Adler V, Yin Z, Tew KD, Ronai Z. Role of redox potential and reactive oxygen species in stress signaling. Oncogene 1999; 18: 6104–6111.

    CAS  PubMed  Google Scholar 

  159. Murphy MP. Nitric oxide and cell death. Biochim Biophys Acta 1999; 1411: 401–414.

    CAS  PubMed  Google Scholar 

  160. Spencer NFL, Poynter ME, Im S-Y, Daynes RA. Constitutive activation of NF-KB in an animal model of aging. Internat immunol 1997; 9: 1581–1588.

    CAS  Google Scholar 

  161. Spencer NFL, Daynes RA. IL-12 directly stimulates expression of IL-10 by CDS+ B cells and IL-6 by both CD5+ and CD5- B cells: Possible involvement in age-associated cytokine dysregulation. Int Immunol 1997; 9: 745–754.

    CAS  PubMed  Google Scholar 

  162. Wang S, Wang W, Wesley RA, Danner RL. A Spi binding site of the tumor necrosis factor a promoter functions as a nitric oxide response element. J Biol Chem 1999; 274: 33, 190–33, 193.

    Google Scholar 

  163. Lewis JS, Lee JA, Underwood JCE, et al. Macrophage responses to hypoxia: relevance to disease mechanisms. J Leukoc Biol 1999; 66: 889–900.

    CAS  PubMed  Google Scholar 

  164. Ivan M, Kondo K, Yang H, et al. HIFa targeted for VHL-mediated destruction by proline hydroxylation: Implications for 02 sensing. Science 2001; 292: 464–468.

    CAS  PubMed  Google Scholar 

  165. Jaakkola P, Mole DR, Tian Y-M, et al. Targeting of HIF-a to the von HippelLindau ubiquitylation complex by 02-regulated prolyl hydroxylation. Science 2001; 292: 468–472.

    CAS  PubMed  Google Scholar 

  166. Carta L, Pastorino S, Melillo G, et al. Engineering of macrophages to produce IFN-yin response to hypoxia. J Immunol 2001; 166: 5374–5380.

    CAS  PubMed  Google Scholar 

  167. Hayek MG, Mura C, Wu D, et al. Enhanced expression of inducible cyclooxygenase with age in murine macrophages. J Immunol 1997; 159: 2445–2451.

    CAS  PubMed  Google Scholar 

  168. Wu D, Hayek MG, Meydani SN. Vitamin E and macrophage cyclooxygenase regulation in the aged. J Nutr 2001; 131: 3825–388S.

    Google Scholar 

  169. Mathews CK, van Holde KE. Biochemistry. Redwood City, CA: Benjamin/ Cummings, 1990.

    Google Scholar 

  170. Mayer B, Wu C, Gorren ACF, et al. Tetrahydrobiopterin binding to macrophage inducible nitric oxide synthase: Herne spin shift and dimer stabilization by the potent pterin antagonist 4-amino-tetrahydrobiopterin. Biochemistry 1997; 36: 8422–8427.

    CAS  PubMed  Google Scholar 

  171. Werner-Felmayer G, Werner ER, Fuchs D, et al. Tetrahydrobiopterin-dependent formation of nitrite and nitrate in murine fibroblasts. J Exp Med 1990; 172: 1599–1607.

    CAS  PubMed  Google Scholar 

  172. Schott K, Yodoi J, Schwulera U, Ziegler I. Control of pteridine biosynthesis in the natural killer-like cell line YT. Biochem Biophys Res Communs 1991; 176: 1430–1436.

    CAS  Google Scholar 

  173. Weinberg JB, Misukonis MA, Shami PJ, et al. Human mononuclear phagocyte inducible nitric oxide synthase (iNOS): Analysis of iNOS mRNA, iNOS protein, biopterin, and nitric oxide production by blood monocytes and peritoneal macrophages. Blood 1995; 86: 1184–1195.

    CAS  PubMed  Google Scholar 

  174. Werner ER, Werner-Felmayer G, Fuchs D, et al. Biochemistry and function of pteridine synthesis in human and murine macrophages. Pathobiology 1991; 59: 276–279.

    CAS  PubMed  Google Scholar 

  175. Ding A, Nathan C, Stuehr DJ. Release of reactive nitrogen intermediates and reactive oxygen intermediates from mouse peritoneal macrophages. J Immunol 1988; 141: 2407–2412.

    CAS  PubMed  Google Scholar 

  176. Akarasereenont P, Mitchell JA, Bakhle YS, et al. Comparison of the induction of cyclooxygenase and nitric oxide synthase by endotoxin in endothelial cells and macrophages. Eur J Pharmacol 1994; 273: 121–128.

    Google Scholar 

  177. Swierkosz TA, Mitchell JA, Warner TD, et al. Co-induction of nitric oxide synthase and cyclo-oxygenase: Interactions between nitric oxide and prostanoids. Br J Pharmacol 1995; 114: 1335–1342.

    CAS  PubMed  Google Scholar 

  178. Marotta P, Sautebin L, DiRosa M. Modulation of the induction of nitric oxide synthase by eicosanoids in the murine macrophage cell line J774. Br J Pharmacol 1992; 107: 640–644.

    CAS  PubMed  Google Scholar 

  179. Pang L, Hoult JRS. Repression of inducible nitric oxide synthase and cyclooxygenase-2 by prostaglandin E2 and other cyclic AMP stimulants in J774 macrophages. Biochem Pharmacol 1997; 53: 493–500.

    CAS  PubMed  Google Scholar 

  180. Lin W-W, Chen B-C, Hsu YW, et al. Modulation of iNOS induction by PGE2 in macrophages: distinct susceptibility in murine J774 and RAW 264.7 macrophages. Prostaglandins Lipid Mediator 1999; 58: 87–101.

    CAS  Google Scholar 

  181. Chen B-C, Lin W-W. Pyrimidinoceptor potentiation of macrophage PGE2 release involved in the induction of nitric oxide synthase. Br J Pharmacol 2000; 130: 777–786.

    CAS  PubMed  Google Scholar 

  182. Clancy R, Varenika B, Huang W, et al. Nitric oxide synthase/COX cross-talk: nitric oxide activates COX-1 but inhibits COX-2-derived prostaglandin production. J Immunol 2000; 165: 1582–1587.

    CAS  PubMed  Google Scholar 

  183. Perez-Sala D, Lamas S. Regulation of cyclooxygenase-2 expression by nitric oxide in cells. Antioxid Redox Signal 2001; 3: 231–248.

    CAS  PubMed  Google Scholar 

  184. Galea E. Feinstein DL. Regulation of the expression of the inflammatory nitric oxide synthase (NOS2) by cyclic AMP. FASEB J 1999; 13: 2125–2137.

    CAS  PubMed  Google Scholar 

  185. Okado-Matsumoto A, Matsumoto A, Fujii J, Taniguchi N. Effect of cAMP on inducible nitric oxide synthase gene expression: Its dual and cell-specific functions. Antioxid Redox Signal 2000; 2: 631–642.

    CAS  Google Scholar 

  186. Mestre JR, Rivadeneira DE, Mackrell PJ, et al. Overlapping CRE and E-box promoter elements can independently regulate COX-2 gene transcription in macrophages. FEBS Lett 2001; 496: 147–151.

    CAS  PubMed  Google Scholar 

  187. Borrelli E, Montmayeur J-P, Foulkes NS, Sassone-Corsi P. Signal transduction and gene control: the cAMP pathway. Crit Rev Oncogen 1992; 3: 321–338.

    CAS  Google Scholar 

  188. Subbaramaiah K, Chung WJ, Dannenberg AJ. Ceramide regulates the transcription of cyclooxygenase-2. J Biol Chem 1998; 273: 32, 943–32, 949.

    Google Scholar 

  189. Niiro H, Otsuka T, Izuhara K, et al. Regulation by interleukin-10 and interleukin-4 of cyclooxygenase-2 expression in human neutrophils. Blood 1997; 89: 1621–1628.

    CAS  PubMed  Google Scholar 

  190. Hobbs MV, Weigle WO, Noonan DJ, et al. Patterns of cytokine gene expression by CD4+ T cells from young and old mice. J Immunol 1993; 150: 3602–3614.

    CAS  PubMed  Google Scholar 

  191. Hobbs MV, Weigle WO, Ernst DN. Interleukin-10 production by splenic CD4+ cells and cell subsets from young and old mice. Cell Immunol 1994; 154: 264–272.

    CAS  PubMed  Google Scholar 

  192. Castle SC, Uyemura K, Crawford W, et al. Age-related impaired proliferation of peripheral blood mononuclear cells is associated with an increase in both IL-10 and IL-12. Exp Gerontol 1999; 34: 243–252.

    CAS  PubMed  Google Scholar 

  193. Rink L, Cakman I, Kirchner H. Altered cytokine production in the elderly. Mech Ageing Dev 1998; 102: 199–209.

    CAS  PubMed  Google Scholar 

  194. Mu XY, Thoman ML. The age-dependent cytokine production by murine CD8+ T cells as determined by four-color flow cytometry analysis. J Gerontol Biol Sci Med Sci 1999; 54: 116–123.

    Google Scholar 

  195. Fernandez-Botran R, Chilton PM, Ma Y, et al. Control of the production of soluble interleukin-4 receptors: Implications in immunoregulation. J Leukoc Biol 1996; 59: 499–504.

    CAS  PubMed  Google Scholar 

  196. Zidek Z. Role of cytokines in the modulation of nitric oxide production by cyclic AMP. Eur Cytokine Netw 2001; 12: 22–32.

    CAS  PubMed  Google Scholar 

  197. Kizaki T, Ookawara T, Oh-Ishi S, et al. An increase in basal glucocorticoid concentration with age induces suppressor macrophages with high-density FcyRII/ III. Immunology 1998; 93: 409–414.

    CAS  PubMed  Google Scholar 

  198. Metzger Z, Hoffeld JT, Oppenheim JJ. Macrophage-mediated suppression. I. Evidence for participation of both hydrogen peroxide and prostaglandins in suppression of murine lymphocyte proliferation. J Immunol 1980; 124: 983–991.

    CAS  PubMed  Google Scholar 

  199. Lysle DT, How T. Endogenous opioids regulate the expression of inducible nitric oxide synthase by splenocytes. J Pharmacol Exp Therap 1999; 288: 502–508.

    CAS  Google Scholar 

  200. Schneider GM, Lysle DT. Role of central mu-opioid receptors in the modulation of nitric oxide production by splenocytes. J Neuroimmunol 1998; 89: 150–159.

    CAS  PubMed  Google Scholar 

  201. Goldsby RA, Kindt TJ, Osborne BA. Kuby Immunology, 4th ed. New York: Freeman 2000: 373–374.

    Google Scholar 

  202. Horwitz AH, Williams RE, Liu PS, Nadell R. Bactericidal/permeability increasing protein inhibits growth of a strain of Acholeplasma lidlawii and L forms of gram-positive bacteria Staphylococcus aureus and Staphylococcus pyogenes. Antimicrob Agents Chemother 1999; 43: 2314–2319.

    CAS  PubMed Central  PubMed  Google Scholar 

  203. Hackam DJ, Rotstein OD, Schreiber AD, et al. V-SNARE-dependent secretion is required for phagocytosis. Proc Natl Acad Sci USA 1998; 95: 11, 691–11, 696.

    Google Scholar 

  204. Mollinedo F, Borregaard N, Boxer LA. Novel trends in neutrophil structure, function and development. Immunol Today 1999; 20: 535–537.

    CAS  PubMed  Google Scholar 

  205. Miller RA, Britigan BE. The formation and biologic significance of phagocyte-derived oxidants. J Invest Med 1995; 43: 39–49.

    CAS  Google Scholar 

  206. Murray HW, Teitelbaum RF. L-arginine-dependent reactive nitrogen intermediates and the antimicrobial effect of activated human mononuclear phagocytes. J Infect Dis 1992; 165: 513–517.

    CAS  PubMed  Google Scholar 

  207. Witztum JL, Steinberg D. Role of oxidized low density lipoprotein in atherogenesis. J Clin Invest 1991; 88: 1785–1792.

    CAS  PubMed Central  PubMed  Google Scholar 

  208. Borregaard N, Cowland JB. Granules of the human neutrophilic polymorphonuclear leukocyte. Blood 1997; 89: 3503–3521.

    CAS  PubMed  Google Scholar 

  209. Chertov O, Yang D, Howard OMZ, Oppenheim JJ. Leukocyte granule proteins mobilize innate host defenses and adaptive immune responses. Immunol Rev 2000; 177: 68–78.

    CAS  PubMed  Google Scholar 

  210. Gullberg U, Bengtsson N, Bulow E, et al. Processing and targeting of granule proteins in human neutrophils. J Immunol Meth 1999; 232: 201–210.

    CAS  Google Scholar 

  211. Cowland JB, Borregaard N. The individual regulation of granule protein mRNA levels during neutrophil maturation explains the heterogeneity of neutrophil granules. J Leukoc Biol 1999; 66: 989–995.

    CAS  PubMed  Google Scholar 

  212. Cassatella MA. Production of cytokines by polymorphonuclear neutrophils. In: Gabrilovich DI, ed. The Neutrophils: New Outlook for Old Cells. London: Imperial College Press, 1999: 151–229.

    Google Scholar 

  213. Walzog B, Weinmann P, Jeblonski F, et al. A role for 132 integrins (CD 11/CD 18) in the regulation of cytokine gene expression of polymorphonuclear neutrophils during the inflammatory response. FASEB J 1999; 13: 1855–1865.

    CAS  PubMed  Google Scholar 

  214. Wahlgren M, Abkams JS, Fernandez V, et al. Adhesion of Plasmodium falciparum-infected erythrocytes to human cells and secretion of cytokines IL-1 beta, IL-1RA, IL-6, IL-8, IL-10, TNF beta, TNF alpha, G-CSF, GM-CSF. Scand J Immunol 1995; 42: 626–636.

    CAS  PubMed  Google Scholar 

  215. Kasama T, Strieter RM, Standiford TJ, et al. Expression and regulation of human neutrophil-derived macrophage inflammatory protein 1 alpha. J Exp Med 1993; 178: 63–72.

    CAS  PubMed  Google Scholar 

  216. Kasama T, Strieter RM, Lukacs NW, et al. Regulation of neutrophil-derived chemokine expression by IL-10. J Immunol 1994; 152: 3559–3569.

    CAS  PubMed  Google Scholar 

  217. Cassatella MA, Meda L, Gasperinis S, et al. Interleukin-12 production by human polymorphonuclear leukocytes. Eur J Immunol 1995; 25: 1–5.

    CAS  PubMed  Google Scholar 

  218. Lee A, Whyte MKB, Haslett C. Inhibition of apoptosis and prolongation of neutrophil functional longevity by inflammatory mediators. J Leukoc Biol 1993; 54: 283–289.

    CAS  PubMed  Google Scholar 

  219. Hirano S. Migratory responses of PMN after intraperitoneal and intratracheal administration of lipopolysaccharide. Am J Physiol 1996; 270: 836–845.

    Google Scholar 

  220. Duffey LM, Albright JW, Albright JF. Trypanosoma musculi: Population dynamics of erythrocytes and leukocytes during the course of murine infections. Exp Parasitol 1985; 59: 375–379.

    CAS  PubMed  Google Scholar 

  221. Albright JW, Pierantoni M, Albright JF. Immune and nonimmune regulation of the population of Trypanosoma musculi in infected host mice. Infect Immun 1990; 58: 1757–1762.

    CAS  PubMed Central  PubMed  Google Scholar 

  222. Bliss SK, Gavrilescu LC, Alcaraz A, Denkers EY. Neutrophil depletion during Toxoplasma gondii infection leads to impaired immunity and lethal systemic pathology. Infect Immun 2001; 69: 4898–4905.

    CAS  PubMed Central  PubMed  Google Scholar 

  223. Tateda K, Moore TA, Deng JC, et al. Early recruitment of neutrophils determines subsequent T1/T2 host responses in a murine model of Legionella pneumophila pneumonia. J Immunol 2001; 166: 3355–3361.

    CAS  PubMed  Google Scholar 

  224. Unanue ER. Inter-relationship among macrophages, natural killer cells and neutrophils in early stages of Listeria resistance. Curr Opin Immunol 1997; 9: 35–43.

    CAS  PubMed  Google Scholar 

  225. Chatta GS, Andrews RG, Rodger E, et al. Hematopoietic progenitors and aging: alterations in granulocyte precursors and responsiveness to recombinant human G-CSF, GM-CSF and IL-3. J Gerontol 1993; 48: 207–212.

    Google Scholar 

  226. Butcher S, Chahel H, Lord JM. Ageing and the neutrophil: no appetite for killing? Immunology 2000; 100: 411–416.

    CAS  PubMed  Google Scholar 

  227. MacGregor RR, Shalit M. Neutrophil function in healthy elderly subjects. J Gerontol 1990; 45: 55–61.

    Google Scholar 

  228. Esperaza B, Sanchez M, Ruiz M, et al. Neutrophil function in elderly persons assessed by flow cytometry. Immunol Invest 1996; 25: 185–191.

    Google Scholar 

  229. Mege JL, Capo C, Michel B, et al. Phagocytic cell function in aged subjects. Neutrophil Aging 1998; 9: 217–220.

    Google Scholar 

  230. Fulop T Jr. Foris G, Worum I, Leovey A. Age-dependent alterations of Fc gamma receptor-mediated effector functions on human polymorphonuclear leukocytes. Clin Exp Immunol 1985; 61: 425–432.

    CAS  PubMed Central  PubMed  Google Scholar 

  231. Emmanueli G, Lanzio M, Anfossi T, et al. Influence of age on polymorphonuclear leukocytes in vitro: Phagocytic activity in healthy human subjects. Gerontology 1986; 32: 308–315.

    Google Scholar 

  232. Wenisch C, Patruta S, Daxbock F, et al. Effect of age on human neutrophil function. J Leukoc Biol 2000; 67: 40–45.

    CAS  PubMed  Google Scholar 

  233. Jaconi ME, Lew DP, Carpentier JL, et al. Cytosolic free calcium elevation mediates the phagosome-lysosome fusion during phagocytosis in human neutrophils. J Cell Biol 1990; 110: 1555–1564.

    CAS  PubMed  Google Scholar 

  234. Bengtsson T, Jaconi ME, Gustafson M, et al. Actin dynamics in human neutrophils during adhesion and phagocytosis is controlled by changes in intracellular free calcium. Eur J Cell Biol 1993; 62: 49–58.

    CAS  PubMed  Google Scholar 

  235. Lipschitz DA, Udupa KB, Boxer LA. The role of calcium in the age-related decline of neutrophil function. Blood 1988; 71: 659–665.

    CAS  PubMed  Google Scholar 

  236. Lipschitz DA, Udupa KB, Indelicato SR, Das M. Effect of age on second messenger generation in neutrophils. Blood 1991; 78: 1347–1354.

    CAS  PubMed  Google Scholar 

  237. Fulop T Jr, Varga Z, Csongor J, et al. Age-related impairment in phosphatidylinositol breakdown of polymorphonuclear granulocytes. FEBS Lett 1989; 245: 249–253.

    CAS  PubMed  Google Scholar 

  238. Nagel JE, Pyle RS, Chrest FJ, Adler WH. Oxidative metabolism and bactericidal capacity of polymorphonuclear leukocytes from normal young and aged adults. J Gerontol 1982; 37: 29–35.

    Google Scholar 

  239. Ito Y, Kajkenova O, Feuers RJ, et al. Impaired glutathione peroxidase activity accounts for the age-related accumulation of hydrogen peroxide in activated human neutrophils. J Gerontol Med Sci 1998; 53: 169–175.

    Google Scholar 

  240. Braga PC, Sala MT, Dal Sasso M, et al. Influence of age on oxidative bursts (chemiluminescence) of polymorphonuclear neutrophil leukocytes. Gerontology 1997; 44: 192–201.

    Google Scholar 

  241. Di Lorenzo G, Balisteri CR, Candore G, et al. Ganulocyte and natural killer activity in the elderly. Mech Ageing Dev 1999; 108: 25–38.

    PubMed  Google Scholar 

  242. Nauseef WM. Myeloperoxidase deficiency. Hematol Oncol Clin North Am 1988; 2: 135–158.

    CAS  PubMed  Google Scholar 

  243. Hellstrom I, Hellstrom KE, Pierce GE, Bill AH. Demonstration of cell-bound and humoral immunity against neuroblastoma cells. Proc Natl Acad Sci USA 1968; 60: 1231–1237.

    CAS  PubMed  Google Scholar 

  244. Herberman RB. Cell-mediated immunity to tumor cells. Adv Cancer Res 1974; 19: 207–263.

    CAS  PubMed  Google Scholar 

  245. Herberman RB, ed. Natural Cell-Mediated Immunity Against Tumors. New York: Academic, 1980.

    Google Scholar 

  246. Welsh RM Jr. Cytotoxic cells induced during lymphocyte choriomeningitis virus infection in mice. I. Characterization of NK cell induction. J Exp Med 1978; 146: 163–181.

    Google Scholar 

  247. Hidore MR, Nabavi N, Sonleitner F, Murphy JW. Murine natural killer cells are fungicidal to Cryptococcus neoformans. Infect Immun 1991; 59: 1747–1754.

    CAS  PubMed Central  PubMed  Google Scholar 

  248. Bennett M. Biology and genetics of hybrid resistance. Adv Immunol 1987; 41: 333–445.

    CAS  PubMed  Google Scholar 

  249. Karre K. How to recognize a foreign submarine. Immunol Rev 1997; 155: 5–9.

    CAS  PubMed  Google Scholar 

  250. Lanier LL. Natural killer cells: from no receptors to too many. Immunity 1997; 6: 371–378.

    CAS  PubMed  Google Scholar 

  251. Wherry JC, Schreiber RD, Unanue ER. Regulation of gamma interferon by natural killer cells in scid mice: Roles of tumor necrosis factor and bacterial stimuli. Infect Immun 1991; 59: 1709–1715.

    CAS  PubMed Central  PubMed  Google Scholar 

  252. Bancroft GJ. The role of natural killer cells in innate resistance to infection. Curr Opin Immunol 1993; 5: 503–511.

    CAS  PubMed  Google Scholar 

  253. Fehniger TA, Shah MH, Turner MJ. Differential cytokine and chemokine gene expression by human NK cells following activation with IL-18 or IL-15 in combination with IL-12: Implications for the innate immune response. J Immunol 1999; 162: 4511–4520.

    CAS  PubMed  Google Scholar 

  254. Lanier L. NK cell receptors. Annu Rev Immunol 1998; 16: 359–393.

    CAS  PubMed  Google Scholar 

  255. Moretta A, Biassoni R, Bottino C, Moretta L. Surface receptors delivering opposite signals regulate the function of human NK cells. Sem Immunol 2000; 12: 129–138.

    CAS  Google Scholar 

  256. Vales-Gomez M, Reyburn H, Strominger J. Interaction between the human NK receptors and their ligands. Crit Rev Immunol 2000; 20: 223–244.

    CAS  PubMed  Google Scholar 

  257. Cassatella MA, Angeon I, Cuturi MC, et al. FcyR (CD 16) interaction with ligand induces Cat+ mobilization and phosphoinositide turnover in human natural killer cells. Role of Cat+ in FcyR (CD 16)-induced transcription and expression of lymphokine genes. J Exp Med 1989; 169: 549–567.

    CAS  PubMed  Google Scholar 

  258. Nakamura MC, Nieme EC, Fisher MJ, et al. Mouse Ly 49A interrupts early signaling events in natural killer cell cytotoxicity and functionally associates with the SHP-1 tyrosine phosphatase. J Exp Med 1997; 185: 673–686.

    CAS  PubMed Central  PubMed  Google Scholar 

  259. Mason LH, Gosselin P, Anderson SK, et al. Differential tyrosine phosphorylation of inhibitory versus activating Ly 49 receptors and their recruitment of SHP1 phosphatase. J Immunol 1997; 159: 4187–4194.

    CAS  PubMed  Google Scholar 

  260. George TC, Mason LH, Ortaldo JR, et al. Positive recognition of MHC class I molecules by the Ly 49D receptor of murine NK cells. J Immunol 1999; 162: 2035–2043.

    CAS  PubMed  Google Scholar 

  261. Smith KA, Wu J, Bakker ABH, et al. Ly 49D and LY 49H associate with DAP 12 to form activating receptors. J Immunol 1998; 161: 7–13.

    CAS  PubMed  Google Scholar 

  262. Hanke T, Raulet DH. Cumulative inhibition of NK cells and T cells resulting from engagement of multiple inhibitory Ly 49 receptors. J Immunol 2001; 166: 3002–3007.

    CAS  PubMed  Google Scholar 

  263. Ortaldo JR, Bere EW, Hodge D, Young HA. Activating Ly-49 NK receptors: Central role in cytokine and chemokine production. J Immunol 2001; 166: 4994–4999.

    CAS  PubMed  Google Scholar 

  264. Bendelac A, Rivera MN, Park S-H. Mouse CD 1-specific NK1 T cells: Development, specificity and function. Annu Rev Immunol 1997; 15: 535–558.

    CAS  Google Scholar 

  265. Kawano T, Cui J, Koezuka Y, et al. CD ld-restricted and TCR-mediated activation of Val4 NKT cells by glycosylceramides. Science 1997; 278: 1626–1629.

    CAS  PubMed  Google Scholar 

  266. Brossay L, Chioda M, Burdin N, et al. CD 1 d-mediated recognition of an agalactosylceramide by natural killer T cells is highly conserved through mammalian evolution. J Exp Med 1998; 188: 1521–1532.

    CAS  PubMed Central  PubMed  Google Scholar 

  267. Hammond KJL, Pellicci DG, Poulton LD, et al. CD 1d-restricted NKT cells: An interstrain comparison. J Immunol 2001; 167: 1164–1173.

    CAS  PubMed  Google Scholar 

  268. Carnaud C, Lee D, Donnars O, et al. Cutting edge: Cross-talk between cells of the innate immune system: NKT cells rapidly activate NK cells. J Immunol 1999; 163: 4647–4650.

    CAS  PubMed  Google Scholar 

  269. Trobonjaca Z, Leithauser F, Moller P, et al. Activating immunity in the liver. I. Liver dendritic cells (but not hepatocytes) are potent activators of IFN-y release by liver NKT cells. J Immunol 2001; 167: 1413–1422.

    CAS  PubMed  Google Scholar 

  270. Schofield L, McConville MJ, Hansen D, et al. CD 1 d-restricted immunoglobulin G formation to GPI-anchored antigens mediated by NKT cells. Science 1999; 283: 225–228.

    CAS  PubMed  Google Scholar 

  271. Warren HS, Kinnear BF, Kastelein RL, Lanier LL. Analysis of the costimulatory role of IL-12 and IL-15 in initiating proliferation of resting (CD 56d“) human NK cells. J Immunol 1996; 156: 3254–3259.

    CAS  PubMed  Google Scholar 

  272. Lin J-X, Leonard WJ. The role of Stat 5a and Stat 513 in signaling by IL-2 family cytokines. Oncogene 2000; 19: 256–276.

    Google Scholar 

  273. Moriggl R, Topham DJ, Teglund S, et al. STAT 5 is required for IL-2-induced cell cycle progression of peripheral T cells. Immunity 1999; 10: 249–259.

    CAS  PubMed  Google Scholar 

  274. Bromberg J, Darnell JE Jr. The role of STATs in transcriptional control and their impact on cellular function. Oncogene 2000; 19: 2468–2473.

    CAS  PubMed  Google Scholar 

  275. Yu CR, Ortaldo JR, Curiel RE, et al. Role of STAT binding site in the regulation of the human perforin promoter. J Immunol 1999; 162: 2785–2790.

    CAS  PubMed  Google Scholar 

  276. Takeda K, Tsutsui H, Yoshimoto T, et al. Defective NK cell activity and Thl response in IL-18-deficient mice. Immunity 1998; 8: 383–390.

    CAS  PubMed  Google Scholar 

  277. Nandi D, Gross JA, Allison JP. CD 28-mediated costimulation is necessary for optimal proliferation of murine NK cells. J Immunol 1994; 152: 3361–3369.

    CAS  PubMed  Google Scholar 

  278. Cheung JC, Koh CY, Gordon BE, et al. The mechanism of activation of NK-cell IFN-gamma production by ligation of CD 28. Mol Immunol 1999; 36: 361–372.

    CAS  PubMed  Google Scholar 

  279. Walker W, Aste-Amezaga M, Kastelein RA, et al. IL-18 and CD 28 use distinct molecular mechanisms to enhance NK cell production of IL-12-induced IFNgamma. J Immunol 1999; 162: 5894–5901.

    CAS  PubMed  Google Scholar 

  280. Cooper MA, Fehniger TA, Ponnappan A, et al. Interleukin-1 beta costimulates interferon-gamma production by human natural killer cells. Eur J Immunol 2001; 31: 792–801.

    CAS  PubMed  Google Scholar 

  281. Voss SD, Daley J, Ritz J, Robertson MJ. Participation of the CD 49 receptor complex in costimulation of human natural killer cells. J Immunol 1998; 160: 1618–1626.

    CAS  PubMed  Google Scholar 

  282. Biron CA. Activation and function of natural killer cell responses during viral infections. Curr Opinion Immunol 1997; 9: 24–34.

    CAS  Google Scholar 

  283. Brown MG, Dokun AO, Hensel JW, et al. Vital involvement of a natural killer cell activation receptor in resistance to viral infection. Science 2001; 292: 934–937.

    CAS  PubMed  Google Scholar 

  284. Lieberman N, Mandelboim O. The role of NK cells in innate immunity. In: Keisari Y, Ofek I, eds.The Biology and Pathology of Innate Immunity Mechanisms. New York: Kluwer Academic/Plenum, 2000: 137–145.

    Google Scholar 

  285. Kos FJ, Engleman EG. Requirement for natural killer cells in the induction of cytotoxic T cells. J Immunol 1995; 155: 578–584.

    CAS  PubMed  Google Scholar 

  286. Scharton-Kersten TM, Sher A. Role of natural killer cells in innate resistance to protozoan infections. Curr Opinion Immunol 1997; 9: 44–51.

    CAS  Google Scholar 

  287. Albright JW, Hatcher FM, Albright JF. Interaction between murine natural killer cells and trypanosomes of different species. Infect Immun 1994; 44: 315–319.

    Google Scholar 

  288. Albright JW, Munger, WE, Henkart PA, et al. The toxicity of rat large granular lymphocyte tumor cells and their cytoplasmic granules for rodent and African trypanosomes. J Immunol 1988; 140: 2774–2778.

    CAS  PubMed  Google Scholar 

  289. Rose ME, Hesketh P, Wakelin D. Cytotoxic effects of natural killer cells have no significant role in controlling infection with the intracellular protozoan Eimeria veriformis. Infect Immun 1995; 63: 3711–3714.

    CAS  PubMed Central  PubMed  Google Scholar 

  290. Johnson LL, Sayles PC. Strong cytolytic activity of natural killer cells is neither necessary or sufficient for preimmune resistance to Toxoplasma gondii infection. Nat Immun 1995; 14: 209–215.

    CAS  PubMed  Google Scholar 

  291. Pawelec G, Solana R, Remarque E, Mariani E. Impact of aging on innate immunity. J Leukoc Biol 1998; 64: 703–712.

    CAS  PubMed  Google Scholar 

  292. Solana R, Mariani E. NK and NK/T cells in human senescence. Vaccine 2000; 18: 1613–1620.

    CAS  PubMed  Google Scholar 

  293. Vitale M, Zamai L, Neri LM, et al. The impairment of natural killer function in the healthy aged is due to a post binding deficient mechanism. Cell Immunol 1992; 145: 1–10.

    CAS  PubMed  Google Scholar 

  294. Mariani E, Roda P, Mariani AR, et al. Age-associated changes in CD8+ and CD 16+ cell reactivity: Clonal analysis. Clin Exp Immunol 1990; 81: 479–484.

    CAS  PubMed Central  PubMed  Google Scholar 

  295. Rukavina D, Laskarin G, Rubesa G, et al. Age-related decline of perform expression in human cytotoxic T lymphocytes and natural killer cells. Blood 1998; 92: 2410–2420.

    CAS  PubMed  Google Scholar 

  296. Mariani E, Sgobbi S, Meneghetti A, et al. Performs in human cytolytic cells: the effect of age. Mech Ageing Dev 1996; 92: 195–209.

    CAS  PubMed  Google Scholar 

  297. Mariani E, Mariani AR, Meneghett A, et al. Age-dependent decreases of NK cell phosphoinositide turnover during spontaneous but not Fc-mediated cytolytic activity. Internat Immunol 1998; 10: 981–989.

    CAS  Google Scholar 

  298. Hsueh C-M, Chen S-F, Ghanta VK, Hiramoto RN. Involvement of cytokine gene expression in the age-dependent decline of NK cell response. Cell Immunol 1996; 173: 221–229.

    CAS  PubMed  Google Scholar 

  299. Krishnaraj R, Bhooma T. Cytokine sensitivity of human NK cells during 1996; 50: 59–63.

    CAS  Google Scholar 

  300. McNerlan SE, Rea IM, Alexander HD, Morris TCM. Changes in natural killer cells, the CD 57 CD 8 subset, and related cytokines in healthy aging. J Clin Immunol 1998; 18: 31–38.

    CAS  PubMed  Google Scholar 

  301. Rajagopalan S, Fu J, Long EO. Cutting edge: Induction of IFN-7 production but not cytotoxicity by the killer cell Ig-like receptor KIR2DL4 (CD 158d) in resting NK cells. J Immunol 2001; 167: 1877–1881.

    CAS  PubMed  Google Scholar 

  302. Borrego F, Alonso MC, Galani MD, et al. NK phenotypic markers and IL-2 response in NK cells from elderly people. Exp Gerontol 1999; 34: 253–265.

    CAS  PubMed  Google Scholar 

  303. Boles KS, Stepp SE, Bennett M, et al. 2B4 (CD244) and CS 1: Novel members of the CD2 subset of the immunoglobulin superfamily molecules expressed on natural killer cells and other leukocytes. Immunol Rev 2001; 181: 234–249.

    CAS  PubMed  Google Scholar 

  304. Yamauchi A, Bloom ET. Control of cell cycle progression in human natural killer cells through redox regulation of expression and phosphorylation of retinoblastoma gene product protein. Blood 1997; 89: 4092–4099.

    CAS  PubMed  Google Scholar 

  305. Albright JW, Albright JF. Age-associated decline in natural killer (NK) activity reflects primarily a defect in function of NK cells. Mech Ageing Dev 1985; 31: 295–306.

    CAS  PubMed  Google Scholar 

  306. Saxena RK, Saxena QB, Adler WH. Interleukin-2-induced activation of natural killer activity in spleen cells from old and young mice. Immunology 1984; 51: 719–726.

    CAS  PubMed  Google Scholar 

  307. Albright, JW, Albright JF. Age-associated impairment of murine natural killer activity. Proc Natl Acad Sci USA 1983; 80: 6371–6375.

    CAS  PubMed  Google Scholar 

  308. Plett A, Murasko DM. Genetic differences in the age-associated decrease in inducibility of natural killer cells by interferon-alpha/beta. Mech Ageing Dev 2000; 112: 197–215.

    CAS  PubMed  Google Scholar 

  309. Albright JW, Bream J, Bere W, et al. Aging of innate immunity: Functional comparisons of NK/LAK cells obtained from bulk cultures of young and aged mouse spleen cells in high concentrations of interleukin-2. J Immunol (submitted).

    Google Scholar 

  310. Fischer B, von Knethen A, Brune B. Dualism of oxidized lipoproteins in provoking and attenuating the oxidative burst in macrophages: Role of peroxisome proliferator-activated receptor-y. J Immunol 2002; 168: 2828–2834.

    CAS  PubMed  Google Scholar 

  311. Cunard R, Ricote M, DiCampli D, et al. Regulation of cytokine expression by ligands of peroxisome proliferator-activated receptors. J Immunol 2002; 168: 2795–2802.

    CAS  PubMed  Google Scholar 

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    Joseph F. Albright PhD & Julia W. Albright PhD

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Albright, J.F., Albright, J.W. (2003). Senescence of Natural/Innate Resistance to Infection. In: Aging, Immunity, and Infection. Infectious Disease. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-402-3_3

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  • DOI: https://doi.org/10.1007/978-1-59259-402-3_3

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