Acute lung inflammation in septic shock of the cytokine release induced by bacterial superantigens

  • Brigitte Neumann
  • Bernhard Holzmann
Part of the Progress in Inflammation Research book series (PIR)


A group of bacterial and viral proteins termed superantigens share the ability to associate with T cell receptor (TCR) and major histocompatibility complex (MHC) class II molecules, generating unique multimeric protein complexes that trigger polyclonal T cell activation [1–4]. Members of the superantigen family include bacterial exotoxins like staphylococcal enterotoxins and toxic shock syndrome toxin-1 (TSST-1), proteins encoded by viral genomes, and retroviral products from mouse mammary tumor viruses [1, 5, 6]. The mechanisms by which superantigens stimulate T cells differ from those of conventional antigens, which require endocytosis and proteolytic processing for presentation of MHC-bound antigenic peptides to T lymphocytes. In contrast, superantigens interact with MHC class II molecules as intact proteins at a site distinct from the peptide binding groove without conformational changes of MHC proteins or superantigens occurring upon complex formation (Fig. 1) [7–13]. The superantigen binding region of MHC class II proteins seems to be conserved among different mammalian haplotypes since superantigens bind to murine, rat, and human class II molecules [3, 14].


Lung Injury Acute Lung Injury Adult Respiratory Distress Syndrome Mouse Mammary Tumor Virus Staphylococcal Enterotoxin 
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  1. 1.
    Acha-Orbea H, Held W, Waanders GA, Shakhov AN, Scarpellino L, Lees RK, MacDonald HR (1993) Exogenous and endogenous mouse mammary tumor virus super-antigens. Immunol Rev 131: 5–25PubMedCrossRefGoogle Scholar
  2. 2.
    Herman A, Kappler JM, Marrack P, Pullen AM (1991) Superantigens: mechanisms of Tcell stimulation and role in immune responses. Annu Rev Immunol 9: 745–772PubMedCrossRefGoogle Scholar
  3. 3.
    Herrmann T, MacDonald HR (1991) T cell recognition of superantigens. Curr Top Microbiol Immunol 174: 21–38PubMedCrossRefGoogle Scholar
  4. 4.
    Heeg K, Miethke T, Wagner H (1996) Superantigen-mediated lethal shock: the functional state of ligand-reactive T cells. Curr Top Microbiol Immunol 216: 83–100PubMedCrossRefGoogle Scholar
  5. 5.
    Marrack P, Kappler J (1990) The staphylococcal enterotoxins and their relatives. Science 248: 705–711PubMedCrossRefGoogle Scholar
  6. 6.
    Marrack P, Winslow GM, Choi Y, Scherer M, Pullen A, White J, Kappler JW (1993) The bacterial and mouse mammary tumor virus superantigens; two different families of proteins with the same functions Immunol Rev 131: 79–92PubMedCrossRefGoogle Scholar
  7. 7.
    Carlsson R, Fischer H, Sjögren HO (1988) Binding of staphylococcal enterotoxin A to accessory cells is a requirement for its ability to acivate human T cells. J Immunol 140: 2484–2488PubMedGoogle Scholar
  8. 8.
    Mollick JA, Cook RG, Rich RR (1989) Class II MHC molecules are specific receptors for staphylococcus enterotoxin A. Science 244: 817–820PubMedCrossRefGoogle Scholar
  9. 9.
    Torres BA, Griggs ND, Johnson HM (1993) Bacterial and retroviral superantigens share a common binding region on class II MHC antigens. Nature 364: 152–154PubMedCrossRefGoogle Scholar
  10. 10.
    Thibodeau J, Labrecque N, Denis F, Huber BT, Sekaly RP (1994) Binding sites for bacterial and endogenous retroviral superantigens can be dissociated on major histocompatibility complex class II molecules. J Exp Med 179: 1029–1034PubMedCrossRefGoogle Scholar
  11. 11.
    Mottershead DG, Hsu PN, Urban RG, Strominger JL, Huber BT (1995) Direct binding of the Mtv7 superantigen (M1s-1) to soluble MHC class II molecules. Immunity 2: 149— 154PubMedCrossRefGoogle Scholar
  12. 12.
    Jardetzky TS, Brown JH, Gorga JC, Stern LJ, Urban RG, Chi Y, Stauffacher C, Strominger JL, Wiley DC (1994) Three-dimensional structure of a human class II histocompatibility molecule comlexed with superantigen. Nature 368: 711–718PubMedCrossRefGoogle Scholar
  13. 13.
    Dellabona P, Peccoud J, Kappler JW, Marrack P, Benoist C, Mathis D (1990) Super-antigens interact with MHC class II molecules outside of the antigen groove. Cell 62: 1115–1121PubMedCrossRefGoogle Scholar
  14. 14.
    Fraser JD (1989) High-affinity binding of staphylococcal enterotoxins A and B to HLA-DR. Nature 339: 221–223PubMedCrossRefGoogle Scholar
  15. 15.
    Scholl PR, Diez A, Geha RS (1989) Staphylococcal enterotoxin B and toxic shock syndrome toxin-1 bind to distinct sites on HLA-DR and HLA-DQ molecules. J Immunol 143: 2583–2588PubMedGoogle Scholar
  16. 16.
    Abrahamsen L, Dohlsten M, Segren S, Björk P, Jonsson E, Kalland T (1995) Characterization of two distinct MHC class II binding sites in the superantigen staphylococcal enterotoxin A. EMBO J 14: 2978–2986Google Scholar
  17. 17.
    Hudson KR, Tiedemann RE, Urban RG, Lowe SC, Strominger JL, Fraser JD (1995) Staphylococcal enterotoxin A has two cooperative binding sites on major histocompatibility complex class II. J Exp Med 182: 711–720PubMedCrossRefGoogle Scholar
  18. 18.
    Kozono H, Parker D, White J, Marrack P, Kappler J (1995) Multiple binding sites for bacterial superantigens on soluble class II MHC molecules. Immunity 3: 187–196PubMedCrossRefGoogle Scholar
  19. 19.
    Cantor H, Crump AL, Raman VK, Liu H, Markowitz JS, Grusby MJ, Glimcher LH (1993) Immunoregulatory effects of superantigens: interactions of staphylococcal enterotoxins with host MHC and non-MHC products. Immunol Rev 131: 27–42PubMedCrossRefGoogle Scholar
  20. 20.
    Avery AC, Markowitz JS, Grusby MJ, Glimcher LH, Cantor H (1994) Activation of T cells by superantigen in class II-negative mice. J Immunol 153: 4853–4861PubMedGoogle Scholar
  21. 21.
    Fleischer B, Schrezenmeier H (1988) T cell stimulation by staphylococcal enterotoxins. Clonally variable response and requirement for major histocompatibility complex class II molecules on accessory or target cells. J Exp Med 167: 1697–1707PubMedCrossRefGoogle Scholar
  22. 22.
    Irwin MJ, Hudson KR, Ames KT, Fraser JD, Gascoigne NRJ (1993) T-cell receptor β-chain binding to enterotoxin superantigens. Immunol Rev 131: 61–78PubMedCrossRefGoogle Scholar
  23. 23.
    Seth A, Stern LJ, Ottenhoff THM, Engel I, Owen MJ, Lamb JR, Klausner RD, Wiley D (1994) Binary and ternary complexes between T cell receptor, class II MHC and super-antigen in vitro. Nature 369: 324–327CrossRefGoogle Scholar
  24. 24.
    Miethke T, Wahl C, Holzmann B, Heeg K, Wagner H (1993) Bacterial superantigens induce rapid and TCR VP-selective downregulation of L-selectin (gp90Mel14) in vivo. J Immunol 151: 6777–6782Google Scholar
  25. 25.
    Gaus H, Miethke T, Wagner H, Heeg K (1994) Superantigen-induced anergy of Vβ8+ CD4+ T cells induces functional but nonproliferative T cells in vivo. Immunology 83: 333–340Google Scholar
  26. 26.
    Miethke T, Wahl C, Heeg K, Echtenacher B, Krammer PH, Wagner H (1992) T-cell mediated lethal shock triggered in mice by the superantigen staphylococcal enterotoxin B: critical role of tumor necrosis factor. J Exp Med 175: 91–98PubMedCrossRefGoogle Scholar
  27. 27.
    Miethke T, Wahl C, Regele D, Gaus H, Heeg K, Wagner H (1993) Superantigen mediated shock: a cytokine release syndrome. Immunobiology 189: 270–284PubMedCrossRefGoogle Scholar
  28. 28.
    Aroeira LS, Williams O, Lozano EG, Martinez-A C (1994) Age-dependent changes in the response to staphylococcal enterotoxin B. Int Immunol 6: 1555–1560PubMedCrossRefGoogle Scholar
  29. 29.
    Florquin S, Amraoui Z, Dubois C, Decuyper J, Goldman M (1994) The protective role of endogenously synthesized nitric oxide in staphylococcal enterotoxin B-induced shock in mice. J Exp Med 180: 1153–1158PubMedCrossRefGoogle Scholar
  30. 30.
    Gonzalo JA, Gonzalez-Garcia A, Martinez C, Kroemer G (1993) Glucocorticoid-mediated control of the activation and clonal deletion of peripheral T cells in vivo. J Exp Med 177: 1239–1246Google Scholar
  31. 31.
    Stiles BG, Bavari S, Krakauer T, Ulrich RG (1993) Toxicity of staphylococcal entero-toxins potentiated by lipopolysaccharide: Major histocompatibility complex class II molecule dependency and cytokine release. Infect Immun 61: 5333–5338PubMedGoogle Scholar
  32. 32.
    Blank C, Luz A, Bendigs S, Erdmann A, Wagner H, Heeg K (1997) Superantigen and endotoxin synergize in the induction of lethal shock. Eur J Immunol 27: 825–833PubMedCrossRefGoogle Scholar
  33. 33.
    Pfeffer K, Matsuyama T, Kündig TM, Wakeham A, Kishihara K, Shahinian A, Wiegmann K, Ohashi PS, Krönke M, Mak TW (1993) Mice deficient for the 55-kd tumor necrosis factor receptor are resistant to endotoxic shock, yet succumb to L monocytogenes infection. Cell 73: 457–467PubMedCrossRefGoogle Scholar
  34. 34.
    Rothe J, Lesslauer W, Lötscher H, Lang Y, Koebel P, Köntgen F, Althage A, Zinkernagel R, Steinmetz M, Bluethmann H (1993) Mice lacking the tumour necrosis factor receptor 1 are resistant to TNF-mediated toxicity but highly susceptible to infection by Listeria monocytogenens. Nature 364: 798–802PubMedCrossRefGoogle Scholar
  35. 35.
    Xu H, Gonzalo JA, Pierre YS, Williams IR, Kupper TS, Cotran RS, Springer TA, Gutierrez Ramos JC (1994) Leukocytosis and resistance to septic shock in intercellular adhesion molecule 1-deficient mice. J Exp Med 180: 95–109PubMedCrossRefGoogle Scholar
  36. 36.
    Freudenberg MA, Keppler D, Galanos C (1986) Requirement for lipopolysaccharideresponsive macrophages in galactosamine-induced sensitization to endotoxin. Infect Immun 51: 891–895PubMedGoogle Scholar
  37. 37.
    Beutler B, Milsark IW, Cerami A (1985) Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effect of endotoxin. Science 229: 869–871PubMedCrossRefGoogle Scholar
  38. 38.
    Tracey KJ, Beutler B, Lowry SF, Merryweather J, Wolpe S, Milsark IW, Hariri RJ, Fahey III TJ, Zentella A, Albert JD et al (1986) Shock and tissue injury induced by recombinant human cachectin. Science 234: 470–474PubMedCrossRefGoogle Scholar
  39. 39.
    Neumann B, Engelhardt B, Wagner H, Holzmann B (1997) Induction of acute inflammatory lung injury by staphylococcal enterotoxin B. J Immunol 158: 1862–1871PubMedGoogle Scholar
  40. 40.
    Brigham KL, Meyrick B (1986) Endotoxin and lung injury. Am Rev Respir Dis 133: 913–927PubMedGoogle Scholar
  41. 41.
    DeGrendele HC, Estess P, Siegelman MH (1997) Requirement for CD44 in activated T cell extravasation into an inflammatory site. Science 278: 672–675CrossRefGoogle Scholar
  42. 42.
    Mohamadzadeh M, DeGrendele H, Arizpe H, Estess P, Siegelman M (1998) Proinflammatory stimuli regulate endothelial hyaluronan expression and CD44/HA-dependent primary adhesion. J Clin Invest 101: 97–108PubMedCrossRefGoogle Scholar
  43. 43.
    Vanier LE, Prud’homme GJ (1992) Cyclosporin A markedly enhances superantigen-induced peripheral T cell deletion and inhibits anergy induction. J Exp Med 176: 37–46PubMedCrossRefGoogle Scholar
  44. 44.
    Lawson MA, Maxfield FR (1995) Ca2+- and calcineurin-dependent recycling of an integrin to the front of migrating neutrophils. Nature 377: 75–79PubMedCrossRefGoogle Scholar
  45. 45.
    Windsor ACJ, Mullen PG, Fowler AA, Sugerman HJ (1993) Role of the neutrophil in adult respiratory distress syndrome. Br J Surg 80: 10–17CrossRefGoogle Scholar
  46. 46.
    Weiland JE, Davis WB, Holter JF, Mohammed JR, Dorinsky PM, Gadek JE (1986) Lung neutrophils in the adult respiratory distress syndrome: clinical and pathophysiologic significance. Am Rev Respir Dis 133: 218–225PubMedGoogle Scholar
  47. 47.
    Heflin AC, Brigham KL (1981) Prevention by granulocyte depletion of increased vascular permeability of sheep lung following endotoxemia. J Clin Invest 68: 1253–1260PubMedCrossRefGoogle Scholar
  48. 48.
    Johnson A, Malik AB (1980) Effect of granulocytopenia on extravascular lung water content after microembolization. Am Rev Respir Dis 122: 561–566PubMedGoogle Scholar
  49. 49.
    Stephens KE, Ishizaka A, Wu ZH, Larrick JW, Raffin TA (1988) Granulocyte depletion prevents tumor necrosis factor-mediated acute lung injury in guinea pigs. Am Rev Respir Dis 138: 1300–1307PubMedGoogle Scholar
  50. 50.
    Till GO, Johnson KJ, Kunkel R, Ward PA (1982) Intravascular activation of complement and acute lung injury: dependency on neutrophils and toxic oxygen metabolites. J Clin Invest 69: 1126–1135PubMedCrossRefGoogle Scholar
  51. 51.
    Welsh CH, Lien DC, Worthen GS, Henson PM, Weil JV (1989) Endotoxin-pretreated neutrophils increase pulmonary vascular permeability in dogs. J Appl Physiol 66: 112–119PubMedGoogle Scholar
  52. 52.
    Maunder RJ, Hackman RC, Riff E, Albert RK, Springmeyer SC (1986) Occurrence of the adult respiratory distress syndrome in neutropenic patients. Am Rev Respir Dis 133: 313–316Google Scholar
  53. 53.
    Ognibene FP, Martin SE, Parker MM, Schlesinger T, Roach P, Burch C, Shelhamer JH, Parrillo JE (1986) Adult respiratory distress syndrome in patients with severe neutropenia. New Engl J Med 315: 547–551PubMedCrossRefGoogle Scholar
  54. 54.
    Mulligan MS, Warren JS, Smith CW, Anderson DC, Yeh CG, Rudolph AR, Ward PA (1992) Lung injury after deposition of IgA immune complexes, Requirements for CD18 and L-arginine. J Immunol 148: 3086–3092PubMedGoogle Scholar
  55. 55.
    Johnson KJ, Ward PA, Kunkel RG, Wilson BS (1986) Mediation of IgA induced lung injury in the rat. Role of macrophages and reactive oxygen products. Lab Invest 54: 499–506PubMedGoogle Scholar
  56. 56.
    Tracey KJ, Fong Y, Hesse DG, Manogue KR, Lee AT, Kuo GC, Lowry SF, Cerami A (1987) Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteraemia. Nature 330: 662–664PubMedCrossRefGoogle Scholar
  57. 57.
    Neumann B, Machleidt T, Lifka A, Pfeffer K, Vestweber D, Mak TW, Holzmann B, Krönke M (1996) Crucial role of 55-kilodalton TNF receptor in TNF-induced adhesion molecule expression and leukocyte organ infiltration. J Immunol 156: 1587–1593PubMedGoogle Scholar
  58. 58.
    Remick DG, Strieter RM, Eskandari MK, Nguyen DT, Genord MA, Raiford CL, Kunkel SL (1990) Role of tumor necrosis factor-a in lipopolysaccharide-induced pathologic alterations. Am J Pathol 136: 49–60PubMedGoogle Scholar
  59. 59.
    Anderson BO, Brown JM, Bensard DD, Grosso MA, Banerjee A, Patt A, Whitman GJR, Harken AH (1990) Reversible lung neutrophil accumulation can cause lung injury by elastase-mediated mechanisms. Surgery 108: 262–268PubMedGoogle Scholar
  60. 60.
    Smedly LA, Tonnesen MG, Sandhaus RA, Haslett C, Guthrie LA, Johnston RB, Henson PM, Worthen GS (1986) Neutrophil-mediated injury to endothelial cells. Enhancement by endotoxin and essential role of neutrophil elastase. J Clin Invest 77: 1233–1243PubMedCrossRefGoogle Scholar
  61. 61.
    Sakamaki F, Ishizaka A, Urano T, Sayama K, Nakamura H, Terashima T, Waki Y, Tasa-ka S, Hasegawa N, Sato K et al (1996) Effect of a specific neutrophil elastase inhibitor, ONO-5046, on endotoxin-induced acute lung injury. Am J Respir Crit Care Med 153: 391–397PubMedGoogle Scholar
  62. 62.
    Ricou B, Nicod L, Lacraz S, Welgus HG, Suter PM, Dayer JM (1996) Matrix metalloproteinases and TIMP in acute respiratory distress syndrome. Am J Respir Crit Care Med 154: 346–352PubMedGoogle Scholar
  63. 63.
    Torii K, Iida KI, Miyazaki Y, Saga S, Kondoh Y, Taniguchi H, Taki F, Takagi K, Matsuyama M, Suzuki R (1997) Higher concentrations of matrix metalloproteinases in bronchoalveolar lavage fluid of patients with adult respiratory distress syndrome. Am J Respir Crit Care Med 155: 43–46PubMedGoogle Scholar
  64. 64.
    Delclaux C, d’Ortho MP, Delacourt C, Lebargy F, Brun-Buisson C, Brochard L, Lemaire F, Lafuma C, Harf A (1997) Gelatinases in epithelial lining fluid of patients with adult respiratory distress syndrome. Am J Physiol 272: L442—L451PubMedGoogle Scholar
  65. 65.
    Redl H, Schlag G, Bahrami S, Schade U, Ceska M, Stütz P (1991) Plasma neutrophilactivating peptide-1/interleukin-8 and neutrophil elastase in a primate bacteremia model. J Infect Dis 164: 383–388PubMedCrossRefGoogle Scholar
  66. 66.
    Gando S, Nakanishi Y, Kameue T, Nanzaki S (1995) Soluble thrombomodulin increases in patients with disseminated intravascular coagulation and in those with multiple organ dysfunction syndrome after trauma: Role of neutrophil elastase. J Trauma 39: 660–664PubMedCrossRefGoogle Scholar
  67. 67.
    Duswald KH, Jochum M, Schramm W, Fritz H (1985) Released granulocytic elastase: An indicator of pathobiochemical alterations in septicemia after abdominal surgery. Surgery 98: 892–899PubMedGoogle Scholar
  68. 68.
    Reddy VY, Desrochers PE, Pizzo SV, Gonias SL, Sahakian JA, Levine RL, Weiss SJ (1994) Oxidative dissociation of human a2-macroglobulin tetramers into dysfunctional dimers. J Biol Chem 269: 4683–4691PubMedGoogle Scholar
  69. 69.
    Weiss SJ, Regiani S (1984) Neutrophils degrade subendothelial matrices in the presence of al-proteinase inhibitor: cooperative use of lysosomal proteinases and oxygen metabolites. J Clin Invest 73: 1297–1303PubMedCrossRefGoogle Scholar
  70. 70.
    Ossanna PJ, Test ST, Matheson NR, Regiani S, Weiss SJ (1986) Oxidative regulation of neutrophil elastase-alpha-1-proteinase inhibitor interactions. J Clin Invest 77: 1939–1951PubMedCrossRefGoogle Scholar
  71. 71.
    Johnson KJ, Ward PA (1981) Role of oxygen metabolites in immune complex injury of lung. J Immunol 126: 2365–2369PubMedGoogle Scholar
  72. 72.
    Hart DHL (1984) Polymorphonuclear leukocyte elastase activity is increased by ba-cterial lipopolysaccharide: a response inhibited by glucocorticoids. Blood 63: 421–426PubMedGoogle Scholar
  73. 73.
    Ottonello L, Morone MP, Dapino P, Dallegri F (1995) Tumour necrosis factor alpha-induced oxidative burst in neutrophils adherent to fibronectin: effects of cyclic AMP-elevating agents. Br J Haematol 91: 566–570PubMedCrossRefGoogle Scholar
  74. 74.
    Dusi S, Bianca VD, Donini M, Nadalini KA, Rossi F (1996) Mechanisms of stimulation of the respiratory burst by TNF in nonadherent neutrophils Its independence of lipidic transmembrane signaling and dependence on protein tyrosine phosphorylation and cytoskeleton. J Immunol 157: 4615–4623PubMedGoogle Scholar
  75. 75.
    Klebanoff SJ, Vadas MA, Harlan JM, Sparks LH, Gamble JR, Agosti JM, Waltersdorph AM (1986) Stimulation of neutrophils by tumor necrosis factor. J Immunol 136: 4220–4225PubMedGoogle Scholar
  76. 76.
    Berkow RL, Wang D, Larrick JW, Dodson RW, Howard TH (1987) Enhancement of neutrophil superoxide production by preincubation with recombinant human tumor necrosis factor. J Immunol 139: 3783–3791PubMedGoogle Scholar
  77. 77.
    Simms HH, D’Amico R (1991) Increased PMN CD11b/CD18 expression following post-traumatic ARDS. J Surg Res 50: 362–367PubMedCrossRefGoogle Scholar
  78. 78.
    Kishimoto TK, Jutila MA, Berg EL, Butcher EC (1989) Neutrophil Mac-1 and MEL-14 adhesion proteins inversely regulated by chemotactic factors. Science 245: 1238–1241PubMedCrossRefGoogle Scholar
  79. 79.
    Bainton DF, Miller LJ, Kishimoto TK, Springer TA (1987) Leukocyte adhesion receptors are stored in peroxidase-negative granules of human neutrophils. J Exp Med 166: 1641–1653PubMedCrossRefGoogle Scholar
  80. 80.
    Miller LJ, Bainton DF, Borregaard N, Springer TA (1987) Stimulated mobilization of monocyte Mac-1 and p150,95 adhesion proteins from an intracellular vesicular compartment to the cell surface. J Clin Invest 80: 535–544PubMedCrossRefGoogle Scholar
  81. 81.
    Bevilacqua MP (1993) Endothelial-leukocyte adhesion molecules. Annu Rev Immunol 11: 767–804PubMedCrossRefGoogle Scholar
  82. 82.
    Mulligan MS,Varani J, Dame MK, Lane CL, Smith CW, Anderson DC, Ward PA (1991) Role of endothelial-leukocyte adhesion molecule 1 (ELAM-1) in neutrophil-mediated lung injury in rats. J Clin Invest 88: 1396–1406CrossRefGoogle Scholar
  83. 83.
    Mulligan MS, Watson SR, Fennie C, Ward PA (1993) Protective effects of selectin chimeras in neutrophil-mediated lung injury. J Immunol 151: 6410–6417PubMedGoogle Scholar
  84. 84.
    Mulligan MS, Smith CW, Anderson DC, Todd RF, Miyasaka M, Tamatani T, Issekutz TB, Ward PA (1993) Role of leukocyte adhesion molecules in complement-induced lung injury. J Immunol 150: 2401–2406PubMedGoogle Scholar
  85. 85.
    Mulligan MS, Polley MJ, Bayer RJ, Nunn MF, Paulson JC, Ward PA (1992) Neutrophildependent acute lung injury: requirement for P-selectin (GMP-140). J Clin Invest 90: 1600–1607PubMedCrossRefGoogle Scholar
  86. 86.
    Mulligan MS, Wilson GP, Todd RF, Smith CW, Anderson DC, Varani J, Issekutz TB, Miyasaka M, Tamatani T, Myasaka M (1993) Role of β1, β2 integrins and ICAM-1 in lung injury after deposition of IgG and IgA immune complexes. J Immunol 150: 2407–2417PubMedGoogle Scholar
  87. 87.
    Mulligan MS, Miyasaka M, Tamatani T, Jones ML, Ward PA (1994) Requirement for L-selectin in neutrophil-mediated lung injury in rats. J Immunol 152: 832–840PubMedGoogle Scholar
  88. 88.
    Miller EJ, Cohen AB, Nagao S, Griffith D, Maunder RJ, Martin TR, Weiner-Kronish JP, Sticherling M, Chrisophers E, Matthay MA (1992) Elevated levels of NAP-1/interleukin-8 are present in the airspaces of patients with the adult respiratory distress syndrome and are associated with increased mortality. Am Rev Respir Dis 146: 427–432PubMedGoogle Scholar
  89. 89.
    Miller EJ, Cohen AB, Matthay MA (1996) Increased interleukin-8 concentrations in the pulmonary edema fluid of patients with acute respiratory distress syndrome from sepsis. Crit Care Med 24: 1448–1454PubMedCrossRefGoogle Scholar
  90. 90.
    Donnelly SC, Strieter RM, Kunkel SL, Walz A, Robertson CR, Carter DC, Grant IS, Pollok AJ, Haslett C (1993) Interleukin-8 and development of adult respiratory distress syndrome in at-risk patient groups. Lancet 341: 643–647PubMedCrossRefGoogle Scholar
  91. 91.
    Courtney Broaddus V, Boylan AM, Hoeffel JM, Kim KJ, Sadick M, Chuntharapai A, Hebert CA (1994) Neutralization of IL-8 inhibits neutrophil influx in a rabbit model of endotoxin-induced pleurisy. J Immunol 152: 2960–2967Google Scholar
  92. 92.
    Yokoi K, Mukaida N, Harada A, Watanabe Y, Matsushima K (1997) Prevention of endotoxemia-induced acute respiratory distress syndrome-like lung injury in rabbits by a monoclonal antibody to IL-8. Lab Invest 76: 375–384PubMedGoogle Scholar
  93. 93.
    Bozic CR, Kolakowski LF, Gerard NP, Garcia-Rodriguez C, von Uexkull-Guldenband C, Conklyn MJ, Breslow R, Showell HJ, Gerard C (1995) Expression and biologic characterization of the murine chemokine KC. J Immunol 154: 6048–6057PubMedGoogle Scholar
  94. 94.
    Lee J, Cacalano G, Camerato T, Toy K, Moore MW, Wood WI (1995) Chemokine binding and activities mediated by the mouse IL-8 receptor. J Immunol 155: 2158–2164PubMedGoogle Scholar
  95. 95.
    Frevert CW, Huang S, Danaee H, Paulauskis JD, Kobzik L (1995) Functional characterization of the rat chemokine KC and its importance in neutrophil recruitment in a rat model of pulmonary inflammation. J Immunol 154: 335–344PubMedGoogle Scholar
  96. 96.
    Schmal H, Shanley TP, Jones ML, Friedl HP, Ward PA (1996) Role for macrophage inflammatory protein-2 in lipopolysaccharide-induced lung injury in rats. J Immunol 156: 1963–1972PubMedGoogle Scholar
  97. 97.
    Ulich TR, Howard SC, Remick DG, Wittwer A, Yi ES, Yin S, Guo K, We1ply JK, Williams JH (1995) Intratracheal administration of endotoxin and cytokines VI Antiserum to CINC inhibits acute inflammation. Am J Physiol 268: L245—L250PubMedGoogle Scholar
  98. 98.
    Baggiolini M, Dewald B, Moser B (1994) Interleukin-8 and related chemotactic cytokines — CXC and CC chemokines. Adv Immunol 55: 97–179PubMedCrossRefGoogle Scholar
  99. 99.
    VanOtteren GM, Strieter RM, Kunkel SL, Paine R, Greenberger MJ, Danforth JM, Burdick MD, Standiford TJ (1995) Compartmentalized expression of RANTES in a murine model of endotoxemia. J Immunol 154: 1900–1908Google Scholar
  100. 100.
    Standiford TJ, Kunkel SL, Lukacs NW, Greenberger MJ, Danforth JM, Kunkel RG, Strieter RM (1995) Macrophage inflammatory protein-1a mediates lung leukocyte recruitment, lung capillary leak, and early mortality in murine endotoxemia. J Immunol 155: 1515–1524PubMedGoogle Scholar
  101. 101.
    Bossink AW, Paemen L, Jansen PM, Hack CE, Thijs LG, van Damme J (1995) Plasma levels of the chemokines monocyte chemotactic proteins-1 and -2 are elevated in human sepsis. Blood 86: 3841–3847PubMedGoogle Scholar
  102. 102.
    Jansen PM, van Damme J, Put W, de Jong IW, Taylor FB, Hack CE (1995) Monocyte chemotactic protein 1 is released during lethal and sublethal bacteremia in baboons. J Infect Dis 171: 1640–1642PubMedCrossRefGoogle Scholar
  103. 103.
    Zisman DA, Kunkel SL, Strieter RM, Tsai WC, Bucknell K, Wilkowski J, Standiford TJ (1997) MCP-1 protects mice in lethal endotoxemia. J Clin Invest 99: 2832–2836PubMedCrossRefGoogle Scholar
  104. 104.
    Jones ML, Mulligan MS, Flory CM, Ward PA, Warren JS (1992) Potential role of monocyte chemoattractant protein 1/JE in monocyte/macrophage-dependent IgA immune complex alveolitis in the rat. J Immunol 149: 2147–2154PubMedGoogle Scholar
  105. 105.
    Jiang Y, Beller DI, Frendl G, Graves DT (1992) Monocyte chemoattractant protein-1 regulates adhesion molecule expression and cytokine production in human monocytes. J Immunol 148: 2423–2428PubMedGoogle Scholar
  106. 106.
    Rollins BJ, Walz A, Baggiolini M (1991) Recombinant human MCP-1/JE induces chemotaxis, calcium flux, and the respiratory burst in human monocytes. Blood 78: 1112–1116PubMedGoogle Scholar
  107. 107.
    Echtenacher B, Falk W, Männel DN, Krammer PH (1990) Requirement of endogenous tumor necrosis factor/cachectin for recovery from experimental peritonitis. J Immunol 145: 3762–3766PubMedGoogle Scholar

Copyright information

© Springer Basel AG 1999

Authors and Affiliations

  • Brigitte Neumann
    • 1
  • Bernhard Holzmann
    • 1
  1. 1.Department of Surgery, Klinikum rechts der IsarTechnical University of MunichMunichGermany

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