Lung Surfactant Proteins A and D as Pattern Recognition Proteins

  • Patrick Waters
  • Mudit Vaid
  • Uday Kishore
  • Taruna Madan
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 653)


Lung surfactant proteins A and D belong to a group of soluble humoral pattern recognition receptors, called collectins, which modulate the immune response to microorganisms. They bind essential carbohydrate and lipid antigens found on the surface of microorganisms via low affinity C-type lectin domains and regulate the host’s response by binding to immune cell surface receptors. They form multimeric structures that bind, agglutinate, opsonise and neutralize many different pathogenic microorganisms including bacteria, yeast, fungi and viruses. They modulate the uptake of these microorganisms by phagocytic cells as well as both the inflammatory and the adaptive immune responses. Recent data have also highlighted their involvement in clearance of apoptotic cells, hypersensitivity and a number of lung diseases.


Alveolar Macrophage Surfactant Protein Carbohydrate Recognition Domain Pulmonary Surfactant Protein Lung Surfactant Protein 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Janeway CA, Jr. The immune system evolved to discriminate infectious nonself from noninfectious self. Immunol Today 1992; 13(1):11–16.PubMedGoogle Scholar
  2. 2.
    Kawai T, Akira S. TLR signaling. Semin Immunol 2007; 19(1):24–32.PubMedGoogle Scholar
  3. 3.
    Atkinson TJ. Toll-like receptors, transduction-effector pathways, and disease diversity: evidence of an immunobiological paradigm explaining all human illness? Int Rev Immunol 2008; 27(4):255–281.PubMedGoogle Scholar
  4. 4.
    Kanneganti TD, Lamkanfi M, Nunez G. Intracellular NOD-like receptors in host defense and disease. Immunity 2007; 27(4):549–559.PubMedGoogle Scholar
  5. 5.
    Crouch E, Hartshorn K, Ofek I. Collectins and pulmonary innate immunity. Immunol Rev 2000;173:52–65.PubMedGoogle Scholar
  6. 6.
    Crouch EC. Collectins and pulmonary host defense. Am J Respir Cell Mol Biol 1998; 19(2):177–201.PubMedGoogle Scholar
  7. 7.
    Kishore U, Reid KB. Structures and functions of mammalian collectins. Results Probl Cell Differ 2001; 33:225–248.PubMedGoogle Scholar
  8. 8.
    Holmskov UL. Collectins and collectin receptors in innate immunity. APMIS Suppl 2000; 100:1–59.PubMedGoogle Scholar
  9. 9.
    Ohtani K, Suzuki Y, Eda S et al. Molecular cloning of a novel human collectin from liver (CL-L1). J Biol Chem 1999; 274(19):13681–13689.PubMedGoogle Scholar
  10. 10.
    Ohtani K, Suzuki Y, Eda S et al. The membrane-type collectin CL-P1 is a scavenger receptor on vascular endothelial cells. J Biol Chem 2001; 276(47):44222–44228.PubMedGoogle Scholar
  11. 11.
    Wakamiya N, Suzuki Y. [Molecular cloning of CL-P1 gene]. Seikagaku 2001; 73(3):205–208.PubMedGoogle Scholar
  12. 12.
    Keshi H, Sakamoto T, Kawai T et al. Identification and characterization of a novel human collectin CL-K1. Microbiol Immunol 2006; 50(12):1001–1013.PubMedGoogle Scholar
  13. 13.
    Karinch AM, Floros J. 5′ splicing and allelic variants of the human pulmonary surfactant protein A genes. Am J Respir Cell Mol Biol 1995; 12(1):77–88.PubMedGoogle Scholar
  14. 14.
    Lu J, Willis AC, Reid KB. Purification, characterization and cDNA cloning of human lung surfactant protein D. Biochem J 1992; 284 (Pt 3):795–802.PubMedGoogle Scholar
  15. 15.
    Rust K, Grosso L, Zhang V et al. Human surfactant protein D: SP-D contains a C-type lectin carbohydrate recognition domain. Arch Biochem Biophys 1991; 290(1):116–126.PubMedGoogle Scholar
  16. 16.
    Lim BL, Willis AC, Reid KB et al. Primary structure of bovine collectin-43 (CL-43). Comparison with conglutinin and lung surfactant protein-D. J Biol Chem 1994; 269(16):11820–11824.PubMedGoogle Scholar
  17. 17.
    Hansen S, Holm D, Moeller V et al. CL-46, a novel collectin highly expressed in bovine thymus and liver. J Immunol 2002; l69(10):5726–5734.Google Scholar
  18. 18.
    Kishore U, Greenhough TJ, Waters P et al. Surfactant proteins SP-A and SP-D: structure, function and receptors. Mol Immunol 2006; 43(9):1293–1315.PubMedGoogle Scholar
  19. 19.
    Haagsman HP, Hogenkamp A, van Eijk M et al. Surfactant collectins and innate immunity. Neonatology 2008; 93(4):288–294.PubMedGoogle Scholar
  20. 20.
    Zhang L, Ikegami M, Crouch EC et al. Activity of pulmonary surfactant protein-D (SP-D) in vivo is dependent on oligomeric structure. J Biol Chem 2001; 276(22):19214–19219.PubMedGoogle Scholar
  21. 21.
    Hartshorn KL, White MR, Crouch EC. Contributions of the N-and C-terminal domains of surfactant protein d to the binding, aggregation, and phagocytic uptake of bacteria. Infect Immun 2002; 70(11):6129–6139.PubMedGoogle Scholar
  22. 22.
    Palaniyar N, Zhang L, Kuzmenko A et al. The role of pulmonary collectin N-terminal domains in surfactant structure, function, and homeostasis in vivo. J Biol Chem 2002; 277(30):26971–26979.PubMedGoogle Scholar
  23. 23.
    White MR, Crouch E, Chang D et al. Increased antiviral and opsonic activity of a highly multimerized collectin chimera. Biochem Biophys Res Commun 2001; 286(1):206–213.PubMedGoogle Scholar
  24. 24.
    White MR, Crouch E, Chang D et al. Enhanced antiviral and opsonic activity of a human mannose-binding lectin and surfactant protein D chimera. J Immunol 2000; 165(4):2108–2115.PubMedGoogle Scholar
  25. 25.
    Wang G, Myers C, Mikerov A et al. Effect of cysteine 85 on biochemical properties and biological function of human surfactant protein A variants. Biochemistry 2007; 46(28):8425–8435.PubMedGoogle Scholar
  26. 26.
    Crouch E, Chang D, Rust K et al. Recombinant pulmonary surfactant protein D. Post-translational modification and molecular assembly. J Biol Chem 1994; 269(22):15808–15813.PubMedGoogle Scholar
  27. 27.
    Colley KJ, Baenziger JU. Identification of the post-translational modifications of the corespecific lectin. The corespecific lectin contains hydroxyproline, hydroxylysine, and glucosylgalactosylhydroxylysine residues. J Biol Chem 1987; 262(21):10290–10295.PubMedGoogle Scholar
  28. 28.
    Lu JH, Thiel S, Wiedemann H et al. Binding of the pentamer/hexamer forms of mannan-binding protein to zymosan activates the proenzyme C1r2C1s2 complex, of the classical pathway of complement, without involvement of C1q. J Immunol 1990; l44(6):2287–2294.Google Scholar
  29. 29.
    Voss T, Melchers K, Scheirle G et al. Structural comparison of recombinant pulmonary surfactant protein SP-A derived from two human coding sequences: implications for the chain composition of natural human SP-A. Am J Respir Cell Mol Biol 1991; 4(1):88–94.PubMedGoogle Scholar
  30. 30.
    van Iwaarden JF, van Strijp JA, Visser H et al. Binding of surfactant protein A (SP-A) to herpes simplex virus type 1-infected cells is mediated by the carbohydrate moiety of SP-A. J Biol Chem 1992; 267(35):25039–25043.PubMedGoogle Scholar
  31. 31.
    Ofek I, Mesika A, Kalina M et al. Surfactant protein D enhances phagocytosis and killing of unencapsulated phase variants of Klebsiella pneumoniae. Infect Immun 2001; 69(1):24–33.PubMedGoogle Scholar
  32. 32.
    Hoppe HJ, Reid KB. Trimeric C-type lectin domains in host defence. Structure 1994; 2(12): 1129–1133.PubMedGoogle Scholar
  33. 33.
    Wang JY, Kishore U, Reid KB. A recombinant polypeptide, composed of the alpha-helical neck region and the carbohydrate recognition domain of conglutinin, self-associates to give a functionally intact homotrimer. FEBS Lett 1995; 376(1–2):6–10.PubMedGoogle Scholar
  34. 34.
    Kishore U, Wang JY, Hoppe HJ et al. The alpha-helical neck region of human lung surfactant protein D is essential for the binding of the carbohydrate recognition domains to lipopolysaccharides and phospholipids. Biochem J 1996; 318(Pt 2):505–511.PubMedGoogle Scholar
  35. 35.
    Weis WI, Drickamer K. Trimeric structure of a C-type mannose-binding protein. Structure 1994; 2(12):1227–1240.PubMedGoogle Scholar
  36. 36.
    Drickamer K. Two distinct classes of carbohydrate-recognition domains in animal lectins. J Biol Chem 1988; 263(20):9557–9560.PubMedGoogle Scholar
  37. 37.
    Yoshida T, Tsuruta Y, Iwasaki M et al. SRCL/CL-P1 recognizes GalNAc and a carcinoma-associated antigen, Tn antigen. J Biochem 2003; 133(3):271–277.PubMedGoogle Scholar
  38. 38.
    Drickamer K. Engineering galactose-binding activity into a C-type mannose-binding protein. Nature 1992; 360(6400):183–186.PubMedGoogle Scholar
  39. 39.
    Weis WI, Drickamer K, Hendrickson WA. Structure of a C-type mannose-binding protein complexed with an oligosaccharide. Nature 1992; 360(6400):127–134.PubMedGoogle Scholar
  40. 40.
    Ng KK, Drickamer K, Weis WI. Structural analysis of monosaccharide recognition by rat liver mannose-binding protein. J Biol Chem 1996; 271(2):663–674.PubMedGoogle Scholar
  41. 41.
    Allen MJ, Laederach A, Reilly PJ et al. Polysaccharide recognition by surfactant protein D: novel interactions of a C-type lectin with nonterminal glucosyl residues. Biochemistry 2001; 40(26):7789–7798.PubMedGoogle Scholar
  42. 42.
    Kuroki Y, Akino T. Pulmonary surfactant protein A (SP-A) specifically binds dipalmitoylphosphatidylcholine. J Biol Chem 1991; 266(5):3068–3073.PubMedGoogle Scholar
  43. 43.
    Ogasawara Y, Kuroki Y, Akino T. Pulmonary surfactant protein D specifically binds to phosphatidylinositol. J Biol Chem 1992; 267(29):21244–21249.PubMedGoogle Scholar
  44. 44.
    Persson AV, Gibbons BJ, Shoemaker JD et al. The major glycolipid recognized by SP-D in surfactant is phosphatidylinositol. Biochemistry 1992; 31(48): 12183–12189.PubMedGoogle Scholar
  45. 45.
    Kuroki Y, Gasa S, Ogasawara Y et al. Binding of pulmonary surfactant protein A to galactosylceramide and asialo-GM2. Arch Biochem Biophys 1992; 299(2):261–267.PubMedGoogle Scholar
  46. 46.
    Kuroki Y, Gasa S, Ogasawara Y et al. Binding specificity of lung surfactant protein SP-D for glucosylceramide. Biochem Biophys Res Commun 1992; 187(2):963–969.PubMedGoogle Scholar
  47. 47.
    Suzuki Y, Fujita Y, Kogishi K. Reconstitution of tubular myelin from synthetic lipids and proteins associated with pig pulmonary surfactant. Am Rev Respir Dis 1989; 140(1):75–81.PubMedGoogle Scholar
  48. 48.
    Wright JR, Wager RE, Hawgood S et al. Surfactant apoprotein Mr = 26,000-36,000 enhances uptake of liposomes by type II cells. J Biol Chem 1987; 262(6):2888–2894.PubMedGoogle Scholar
  49. 49.
    Wert SE, Yoshida M, LeVine AM et al. Increased metalloproteinase activity, oxidant production, and emphysema in surfactant protein D gene-inactivated mice. Proc Natl Acad Sci U S A 2000; 97(11):5972–5977.PubMedGoogle Scholar
  50. 50.
    Hakansson K, Lim NK, Hoppe HJ et al. Crystal structure of the trimeric alpha-helical coiled-coil and the three lectin domains of human lung surfactant protein D. Structure 1999; 7(3):255–264.PubMedGoogle Scholar
  51. 51.
    Shrive AK, Tharia HA, Strong P et al. High-resolution structural insights into ligand binding and immune cell recognition by human lung surfactant protein D. J Mol Biol 2003; 331(2):509–523.PubMedGoogle Scholar
  52. 52.
    Ng KK, Park-Snyder S, Weis WI. Ca2+-dependent structural changes in C-type mannose-binding proteins. Biochemistry 1998; 37(51):17965–17976.PubMedGoogle Scholar
  53. 53.
    Leth-Larsen R, Garred P, Jensenius H et al. A common polymorphism in the SFTPD gene influences assembly, function, and concentration of surfactant protein D. J Immunol 2005; 174(3):1532–1538.PubMedGoogle Scholar
  54. 54.
    Turner ST, Chapman AB, Schwartz GL et al. Effects of endothelial nitric oxide synthase, alpha-adducin, and other candidate gene polymorphisms on blood pressure response to hydrochlorothiazide. Am J Hypertens 2003; 16(10):834–839.PubMedGoogle Scholar
  55. 55.
    Bochud PY, Hawn TR, Aderem A. Cutting edge: a Toll-like receptor 2 polymorphism that is associated with lepromatous leprosy is unable to mediate mycobacterial signaling. J Immunol 2003; 170(7):3451–3454.PubMedGoogle Scholar
  56. 56.
    Kiechl S, Lorenz E, Reindl M et al. Toll-like receptor 4 polymorphisms and atherogenesis. N Engl J Med 2002; 347(3):185–192.PubMedGoogle Scholar
  57. 57.
    Crouch EC, Persson A, Griffin GL et al. Interactions of pulmonary surfactant protein D (SP-D) with human blood leukocytes. Am J Respir Cell Mol Biol 1995; 12(4):410–415.PubMedGoogle Scholar
  58. 58.
    Uemura T, Sano H, Katoh T et al. Surfactant protein A without the interruption of Gly-X-Y repeats loses a kink of oligomeric structure and exhibits impaired phospholipid liposome aggregation ability. Biochemistry 2006; 45(48):14543–14551.PubMedGoogle Scholar
  59. 59.
    McNeely TB, Coonrod JD. Aggregation and opsonization of type A but not type B Hemophilus influenzae by surfactant protein A. Am J Respir Cell Mol Biol 1994; 11(1):114–122.PubMedGoogle Scholar
  60. 60.
    Sano H, Sohma H, Muta T et al. Pulmonary surfactant protein A modulates the cellular response to smooth and rough lipopolysaccharides by interaction with CD14. J Immunol 1999; 163(1):387–395.PubMedGoogle Scholar
  61. 61.
    Murakami S, Iwaki D, Mitsuzawa H et al. Surfactant protein A inhibits peptidoglycan-induced tumor necrosis factor-alpha secretion in U937 cells and alveolar macrophages by direct interaction with toll-like receptor 2. J Biol Chem 2002; 277(9):6830–6837.PubMedGoogle Scholar
  62. 62.
    Sato M, Sano H, Iwaki D et al. Direct binding of Toll-like receptor 2 to zymosan, and zymosan-induced NF-kappa B activation and TNF-alpha secretion are down-regulated by lung collectin surfactant protein A. J Immunol 2003; 171(1):417–425.PubMedGoogle Scholar
  63. 63.
    Guillot L, Balloy V, McCormack FX et al. Cutting edge: the immunostimulatory activity of the lung surfactant protein-A involves Toll-like receptor 4. J Immunol 2002; l68(12):5989–5992.Google Scholar
  64. 64.
    Beharka AA, Gaynor CD, Kang BK et al. Pulmonary surfactant protein A up-regulates activity of the mannose receptor, a pattern recognition receptor expressed on human macrophages. J Immunol 2002; 169(7):3565–3573.PubMedGoogle Scholar
  65. 65.
    Kuronuma K, Sano H, Kato K et al. Pulmonary surfactant protein A augments the phagocytosis of Streptococcus pneumoniae by alveolar macrophages through a casein kinase 2-dependent increase of cell surface localization of scavenger receptor A. J Biol Chem 2004; 279(20):21421–21430.PubMedGoogle Scholar
  66. 66.
    Kudo K, Sano H, Takahashi H et al. Pulmonary collectins enhance phagocytosis of Mycobacterium avium through increased activity of mannose receptor. J Immunol 2004; 172(12):7592–7602.PubMedGoogle Scholar
  67. 67.
    Chiba H, Pattanajitvilai S, Evans AJ et al. Human surfactant protein D (SP-D) binds Mycoplasma pneumoniae by high affinity interactions with lipids. J Biol Chem 2002; 277(23):20379–20385.PubMedGoogle Scholar
  68. 68.
    Pasula R, Downing JF, Wright JR et al. Surfactant protein A (SP-A) mediates attachment of Mycobacterium tuberculosis to murine alveolar macrophages. Am J Respir Cell Mol Biol 1997; 17(2):209–217.PubMedGoogle Scholar
  69. 69.
    Ragas A, Roussel L, Puzo G et al. The Mycobacterium tuberculosis cell-surface glycoprotein apa as a potential adhesin to colonize target cells via the innate immune system pulmonary C-type lectin surfactant protein A. J Biol Chem 2007; 282(8):5133–5142.PubMedGoogle Scholar
  70. 70.
    Sidobre S, Puzo G, Riviere M. Lipid-restricted recognition of mycobacterial lipoglycans by human pulmonary surfactant protein A: a surface-plasmon-resonance study. Biochem J 2002; 365(Pt 1): 89–97.PubMedGoogle Scholar
  71. 71.
    Pasula R, Wright JR, Kachel DL et al. Surfactant protein A suppresses reactive nitrogen intermediates by alveolar macrophages in response to Mycobacterium tuberculosis. J Clin Invest 1999; 103(4):483–490.PubMedGoogle Scholar
  72. 72.
    Janssen WJ, McPhillips KA, Dickinson MG et al. Surfactant proteins A and D suppress alveolar macrophage phagocytosis via interaction with SIRP alpha. Am J Respir Grit Care Med 2008; 178(2):158–167.Google Scholar
  73. 73.
    Gold JA, Hoshino Y, Tanaka N et al. Surfactant protein A modulates the inflammatory response in macrophages during tuberculosis. Infect Immun 2004; 72(2):645–650.PubMedGoogle Scholar
  74. 74.
    Ferguson JS, Voelker DR, McCormack FX et al. Surfactant protein D binds to Mycobacterium tuberculosis bacilli and lipoarabinomannan via carbohydrate-lectin interactions resulting in reduced phagocytosis of the bacteria by macrophages. J Immunol 1999; 163(1):312–321.PubMedGoogle Scholar
  75. 75.
    Ferguson JS, Voelker DR, Ufnar JA et al. Surfactant protein D inhibition of human macrophage uptake of Mycobacterium tuberculosis is independent of bacterial agglutination. J Immunol 2002; 168(3):1309–1314.PubMedGoogle Scholar
  76. 76.
    Ferguson JS, Martin JL, Azad AK et al. Surfactant protein D increases fusion of Mycobacterium tuberculosis-containing phagosomes with lysosomes in human macrophages. Infect Immun 2006; 74(12):7005–7009.PubMedGoogle Scholar
  77. 77.
    Downing JF, Pasula R, Wright JR et al. Surfactant protein a promotes attachment of Mycobacterium tuberculosis to alveolar macrophages during infection with human immunodeficiency virus. Proc Natl Acad Sci U S A 1995; 92(11):4848–4852.PubMedGoogle Scholar
  78. 78.
    O’Riordan DM, Standing JE, Kwon KY et al. Surfactant protein D interacts with Pneumocystis carinii and mediates organism adherence to alveolar macrophages. J Clin Invest 1995; 95(6):2699–2710.PubMedGoogle Scholar
  79. 79.
    Linke MJ, Harris CE, Korfhagen TR et al. Immunosuppressed surfactant protein A-deficient mice have increased susceptibility to Pneumocystis carinii infection. J Infect Dis 2001; 183(6):943–952.PubMedGoogle Scholar
  80. 80.
    Atochina EN, Gow AJ, Beck JM et al. Delayed clearance of pneumocystis carinii infection, increased inflammation, and altered nitric oxide metabolism in lungs of surfactant protein-D knockout mice. J Infect Dis 2004; 189(8):1528–1539.PubMedGoogle Scholar
  81. 81.
    Atochina EN, Beck JM, Preston AM et al. Enhanced lung injury and delayed clearance of Pneumocystis carinii in surfactant protein A-deficient mice: attenuation of cytokine responses and reactive oxygen-nitrogen species. Infect Immun 2004; 72(10):6002–6011.PubMedGoogle Scholar
  82. 82.
    Vuk-Pavlovic Z, Standing JE, Crouch EC et al. Carbohydrate recognition domain of surfactant protein D mediates interactions with Pneumocystis carinii glycoprotein A. Am J Respir Cell Mol Biol 2001; 24(4):475–484.PubMedGoogle Scholar
  83. 83.
    Zimmerman PE, Voelker DR, McCormack FX et al. 120-kD surface glycoprotein of Pneumocystis carinii is a ligand for surfactant protein A. J Clin Invest 1992; 89(1): 143–149.PubMedGoogle Scholar
  84. 84.
    Yong SJ, Vuk-Pavlovic Z, Standing JE et al. Surfactant protein D-mediated aggregation of Pneumocystis carinii impairs phagocytosis by alveolar macrophages. Infect Immun 2003; 71(4):1662–1671.PubMedGoogle Scholar
  85. 85.
    Koziel H, Phelps DS, Fishman JA et al. Surfactant protein-A reduces binding and phagocytosis of pneumocystis carinii by human alveolar macrophages in vitro. Am J Respir Cell Mol Biol 1998; 18(6):834–843.PubMedGoogle Scholar
  86. 86.
    Hartshorn KL, White MR, Shepherd V et al. Mechanisms of anti-influenza activity of surfactant proteins A and D: comparison with serum collectins. Am J Physiol 1997; 273(6 Pt 1):L1156–1166.PubMedGoogle Scholar
  87. 87.
    Hartshorn KL, White MR, Voelker DR et al. Mechanism of binding of surfactant protein D to influenza A viruses: importance of binding to haemagglutinin to antiviral activity. Biochem J 2000; 35(1 Pt 2):449–458.Google Scholar
  88. 88.
    Mikerov AN, Wang G, Umstead TM et al. Surfactant protein A2 (SP-A2) variants expressed in CHO cells stimulate phagocytosis of Pseudomonas aeruginosa more than do SP-A1 variants. Infect Immun 2007; 75(3): 1403–1412.PubMedGoogle Scholar
  89. 89.
    LeVine AM, Whitsett JA, Hartshorn KL et al. Surfactant protein D enhances clearance of influenza A virus from the lung in vivo. J Immunol 2001; l67(10):5868–5873.Google Scholar
  90. 90.
    LeVine AM, Hartshorn K, Elliott J et al. Absence of SP-A modulates innate and adaptive defense responses to pulmonary influenza infection. Am J Physiol Lung Cell Mol Physiol 2002; 282(3):L563–572.PubMedGoogle Scholar
  91. 91.
    Hartshorn KL, Crouch EC, White MR et al. Evidence for a protective role of pulmonary surfactant protein D (SP-D) against influenza A viruses. J Clin Invest 1994; 94(1):311–319.PubMedGoogle Scholar
  92. 92.
    Hartshorn KL, Reid KB, White MR et al. Neutrophil deactivation by influenza A viruses: mechanisms of protection after viral opsonization with collectins and hemagglutination-inhibiting antibodies. Blood 1996; 87(8):3450–3461.PubMedGoogle Scholar
  93. 93.
    Malhotra R, Haurum J, Thiel S et al. Pollen grains bind to lung alveolar type II cells (A549) via lung surfactant protein A (SP-A). Biosci Rep 1993; 13(2):79–90.PubMedGoogle Scholar
  94. 94.
    Wang JY, Kishore U, Lim BL et al. Interaction of human lung surfactant proteins A and D with mite (Dermatophagoides pteronyssinus) allergens. Clin Exp Immunol 1996; 106(2):367–373.PubMedGoogle Scholar
  95. 95.
    Madan T, Eggleton P, Kishore U et al. Binding of pulmonary surfactant proteins A and D to Aspergillus fumigatus conidia enhances phagocytosis and killing by human neutrophils and alveolar macrophages. Infect Immun 1997; 65(8):3171–3179.PubMedGoogle Scholar
  96. 96.
    Madan T, Kishore U, Shah A et al. Lung surfactant proteins A and D can inhibit specific IgE binding to the allergens of Aspergillus fumigatus and block allergen-induced histamine release from human basophils. Clin Exp Immunol 1997; 110(2):241–249.PubMedGoogle Scholar
  97. 97.
    Wang JY, Shieh CC, You PF et al. Inhibitory effect of pulmonary surfactant proteins A and D on allergen-induced lymphocyte proliferation and histamine release in children with asthma. Am J Respir Crit Care Med 1998; 158(2):510–518.PubMedGoogle Scholar
  98. 98.
    Deb R, Shakib F, Reid K et al. Major house dust mite allergens Dermatophagoides pteronyssinus 1 and Dermatophagoides farinae 1 degrade and inactivate lung surfactant proteins A and D. J Biol Chem 2007; 282(51):36808–36819.PubMedGoogle Scholar
  99. 99.
    Cheng G, Ueda T, Numao T et al. Increased levels of surfactant protein A and D in bronchoalveolar lavage fluids in patients with bronchial asthma. Eur Respir J 2000; 16(5):831–835.PubMedGoogle Scholar
  100. 100.
    Wang JY, Shieh CC, Yu CK et al. Allergen-induced bronchial inflammation is associated with decreased levels of surfactant proteins A and D in a murine model of asthma. Clin Exp Allergy 2001; 31(4):652–662.PubMedGoogle Scholar
  101. 101.
    Atochina EN, Beers MF, Tomer Y et al. Attenuated allergic airway hyperresponsiveness in C57BL/6 mice is associated with enhanced surfactant protein (SP)-D production following allergic sensitization. Respir Res 2003; 4:15.PubMedGoogle Scholar
  102. 102.
    Schmiedl A, Ochs M, Muhlfeld C et al. Distribution of surfactant proteins in type II pneumocytes of newborn, 14-day old, and adult rats: an immunoelectron microscopic and stereological study. Histochem Cell Biol 2005; 124(6):465–476.PubMedGoogle Scholar
  103. 103.
    Erpenbeck VJ, Schmidt R, Gunther A et al. Surfactant protein levels in bronchoalveolar lavage after segmental allergen challenge in patients with asthma. Allergy 2006; 61(5):598–604.PubMedGoogle Scholar
  104. 104.
    Strong P, Reid KB, Clark H. Intranasal delivery of a truncated recombinant human SP-D is effective at down-regulating allergic hypersensitivity in mice sensitized to allergens of Aspergillus fumigatus. Clin Exp Immunol 2002; 130(1):19–24.PubMedGoogle Scholar
  105. 105.
    Singh M, Madan T, Waters P et al. Protective effects of a recombinant fragment of human surfactant protein D in a murine model of pulmonary hypersensitivity induced by dust mite allergens. Immunol Lett 2003; 86(3):299–307.PubMedGoogle Scholar
  106. 106.
    Takeda K, Miyahara N, Rha YH et al. Surfactant protein D regulates airway function and allergic inflammation through modulation of macrophage function. Am J Respir Crit Care Med 2003; 168(7):783–789.PubMedGoogle Scholar
  107. 107.
    Madan T, Kishore U, Singh M et al. Surfactant proteins A and D protect mice against pulmonary hypersensitivity induced by Aspergillus fumigatus antigens and allergens. J Clin Invest 2001; 107(4):467–475.PubMedGoogle Scholar
  108. 108.
    Brinker KG, Martin E, Borron P et al. Surfactant protein D enhances bacterial antigen presentation by bone marrow-derived dendritic cells. Am J Physiol Lung Cell Mol Physiol 2001; 281(6):L1453–1463.PubMedGoogle Scholar
  109. 109.
    Brinker KG, Garner H, Wright JR. Surfactant protein A modulates the differentiation of murine bone marrow-derived dendritic cells. Am J Physiol Lung Cell Mol Physiol 2003; 284(1):L232–241.PubMedGoogle Scholar
  110. 110.
    Kishore U, Kojouharova MS, Reid KB. Recent progress in the understanding of the structurefunction relationships of the globular head regions of Clq. Immunobiology 2002; 205(4–5):355–364.PubMedGoogle Scholar
  111. 111.
    Liu CF, Chen YL, Chang WT et al. Mite allergen induces nitric oxide production in alveolar macrophage cell lines via CD14/toll-like receptor 4, and is inhibited by surfactant protein D. Clin Exp Allergy 2005; 35(12):1615–1624.PubMedGoogle Scholar
  112. 112.
    Mahajan L, Madan T, Kamal N et al. Recombinant surfactant protein-D selectively increases apoptosis in eosinophils of allergic asthmatics and enhances uptake of apoptotic eosinophils by macrophages. Int Immunol 2008; 20(8):993–1007.PubMedGoogle Scholar
  113. 113.
    Korfhagen TR, Bruno MD, Ross GF et al. Altered surfactant function and structure in SP-A gene targeted mice. Proc Natl Acad Sci U S A 1996; 93(18):9594–9599.PubMedGoogle Scholar
  114. 114.
    Ikegami M, Korfhagen TR, Bruno MD et al. Surfactant metabolism in surfactant protein A-deficient mice. Am J Physiol 1997; 272(3 Pt 1):L479–485.PubMedGoogle Scholar
  115. 115.
    Korfhagen TR, LeVine AM, Whitsett JA. Surfactant protein A (SP-A) gene targeted mice. Biochim Biophys Acta 1998; l408(2–3):296–302.Google Scholar
  116. 116.
    LeVine AM, Whitsett JA, Gwozdz JA et al. Distinct effects of surfactant protein A or D deficiency during bacterial infection on the lung. J Immunol 2000; 165(7):3934–3940.PubMedGoogle Scholar
  117. 117.
    LeVine AM, Whitsett JA. Pulmonary collectins and innate host defense of the lung. Microbes Infect 2001; 3(2):161–166.PubMedGoogle Scholar
  118. 118.
    Zhang S, Chen Y, Potvin E et al. Comparative signaturetagged mutagenesis identifies Pseudomonas factors conferring resistance to the pulmonary collectin SP-A. PLoS Pathog 2005; 1(3):259–268.PubMedGoogle Scholar
  119. 119.
    Zhang S, McCormack FX, Levesque RC et al. The flagellum of Pseudomonas aeruginosa is required for resistance to clearance by surfactant protein A. PLoS ONE 2007; 2(6):e564.PubMedGoogle Scholar
  120. 120.
    Botas C, Poulain F, Akiyama J et al. Altered surfactant homeostasis and alveolar type II cell morphology in mice lacking surfactant protein D. Proc Natl Acad Sci U S A 1998; 95(20):11869–11874.PubMedGoogle Scholar
  121. 121.
    Zhang L, Hartshorn KL, Crouch EC et al. Complementation of pulmonary abnormalities in SP-D(-/-) mice with an SP-D/conglutinin fusion protein. J Biol Chem 2002; 277(25):22453–22459.PubMedGoogle Scholar
  122. 122.
    Dranoff G, Crawford AD, Sadelain M et al. Involvement of granulocyte-macrophage colony-stimulating factor in pulmonary homeostasis. Science 1994; 264(5159):713–716.PubMedGoogle Scholar
  123. 123.
    Ikegami M, Ueda T, Hull W et al. Surfactant metabolism in transgenic mice after granulocyte macrophage-colony stimulating factor ablation. Am J Physiol 1996; 270(4 Pt 1):L650–658.PubMedGoogle Scholar
  124. 124.
    Reed JA, Ikegami M, Robb L et al. Distinct changes in pulmonary surfactant homeostasis in common beta-chain-and GM-CSF-deficient mice. Am J Physiol Lung Cell Mol Physiol 2000; 278(6):L1164–1171.PubMedGoogle Scholar
  125. 125.
    Ochs M, Knudsen L, Allen L et al. GM-CSF mediates alveolar epithelial type II cell changes, but not emphysema-like pathology, in SP-D-deficient mice. Am J Physiol Lung Cell Mol Physiol 2004; 287(6):L1333–1341.PubMedGoogle Scholar
  126. 126.
    Ikegami M, Hull WM, Yoshida M et al. SP-D and GM-CSF regulate surfactant homeostasis via distinct mechanisms. Am J Physiol Lung Cell Mol Physiol 2001; 281(3):L697–703.PubMedGoogle Scholar
  127. 127.
    Hawgood S, Akiyama J, Brown C et al. GM-CSF mediates alveolar macrophage proliferation and type II cell hypertrophy in SP-D gene-targeted mice. Am J Physiol Lung Cell Mol Physiol 2001; 280(6):L1148–1156.PubMedGoogle Scholar
  128. 128.
    Jain D, Atochina-Vasserman E, Kadire H et al. SP-D-deficient mice are resistant to hyperoxia. Am J Physiol Lung Cell Mol Physiol 2007; 292(4):L861–871.PubMedGoogle Scholar
  129. 129.
    Vandivier RW, Ogden CA, Fadok VA et al. Role of surfactant proteins A, D, and C1q in the clearance of apoptotic cells in vivo and in vitro: calreticulin and CD91 as a common collectin receptor complex. J Immunol 2002; l69(7):3978–3986.Google Scholar
  130. 130.
    Madan T, Reid KB, Singh M et al. Susceptibility of mice genetically deficient in the surfactant protein (SP)-A or SP-D gene to pulmonary hypersensitivity induced by antigens and allergens of Aspergillus fumigatus. J Immunol 2005; 174(11):6943–6954.PubMedGoogle Scholar
  131. 131.
    Haczku A, Cao Y, Vass G et al. IL-4 and IL-13 form a negative feedback circuit with surfactant protein-D in the allergic airway response. J Immunol 2006; 176(6):3557–3565.PubMedGoogle Scholar
  132. 132.
    Homer RJ, Zheng T, Chupp G et al. Pulmonary type II cell hypertrophy and pulmonary lipoproteinosis are features of chronic IL-13 exposure. Am J Physiol Lung Cell Mol Physiol 2002; 283(1):L52–59.PubMedGoogle Scholar
  133. 133.
    Schaub B, Westlake RM, He H et al. Surfactant protein D deficiency influences allergic immune responses. Clin Exp Allergy 2004; 34(12):1819–1826.PubMedGoogle Scholar
  134. 134.
    Brandt EB, Mingler MK, Stevenson MD et al. Surfactant protein D alters allergic lung responses in mice and human subjects. J Allergy Clin Immunol 2008; 121(5):1140–1147 e1142.PubMedGoogle Scholar
  135. 135.
    Hawgood S, Ochs M, Jung A et al. Sequential targeted deficiency of SP-A and-D leads to progressive alveolar lipoproteinosis and emphysema. Am J Physiol Lung Cell Mol Physiol 2002; 283(5):L1002–1010.PubMedGoogle Scholar
  136. 136.
    Jung A, Allen L, Nyengaard JR et al. Design-based stereological analysis of the lung parenchymal architecture and alveolar type II cells in surfactant protein A and D double deficient mice. Anat Rec A Discov Mol Cell Evol Biol 2005; 286(2):885–890.PubMedGoogle Scholar
  137. 137.
    Hawgood S, Brown C, Edmondson J et al. Pulmonary collectins modulate strain-specific influenza a virus infection and host responses. J Virol 2004; 78(16):8565–8572.PubMedGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2009

Authors and Affiliations

  • Patrick Waters
    • 1
  • Mudit Vaid
    • 2
  • Uday Kishore
    • 3
  • Taruna Madan
    • 4
  1. 1.Neurosciences Group Department of Clinical Neurolog Weatherall Institute of Molecular MedicineJohn Radcliffe HospitalHeadington, OxfordUK
  2. 2.Department of DermatologyUniversity of AlabamaBirminghamUSA
  3. 3.Laboratory of Human Immunology and Infection Biology Biosciences Division School of Health Sciences and Social CareBrunei UniversityUxbridge, LondonUK
  4. 4.Department of Innate ImmunologyNational Institute for Research in Reproductive HealthMumbaiIndia

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