The Respiratory Burst and Endothelial Cells

  • Aldo Dobrina
  • Pierluigi Patriarca


Neutrophils are the first-line defense of the host against foreign invaders once they have reached the tissues. When at work, however, the neutrophils behave as a double-edged sword. In fact, the reactive oxygen intermediates (ROI) generated by the respiratory burst and the granular components released during degranulation contribute to killing of ingested microorganisms on one side, but, on the other they may damage tissues in both their cellular and extracellular components. Several cell types, including the neutrophils themselves, may be the target of ROI produced by the neutrophil respiratory burst.1 Endothelial cells, a crucial cell type in the interface phenomena between blood and tissues, are among those targets. This chapter first reviews evidence, from both in vitro and in vivo studies, of the involvement of the neutrophil respiratory burst in endothelial cell damage, followed by a discussion of the possible role of such a damage in human pathology.


Endothelial Cell Phorbol Myristate Acetate Respiratory Burst Chronic Granulomatous Disease Neutrophil Elastase 


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  1. 1.
    Clark RA: Extracellular effects of the myeloperoxidase-hydrogen peroxide-halide system. Adv Inflammation Res 5: 107–146, 1983.Google Scholar
  2. 2.
    Sacks T, Moldow CF, Craddock PR, et al: Oxygen radicals mediate endothelial cell damage by complement-stimulated granulocytes. An in vitro model of immune vascular damage. J Clin Invest 61: 1161–1167, 1978.PubMedGoogle Scholar
  3. 3.
    Yamada O, Moldow CF, Sacks T, et al: Deleterious effects of endotoxin on cultured endothelial cells. An in vitro model of vascular injury. Inflammation 5: 115–126, 1981.PubMedGoogle Scholar
  4. 4.
    Weiss SJ, Young J, Lo Buglio AF, et al: Role of hydrogen peroxide in neutrophilmediated destruction of cultured endothelial cells. J Clin Invest 68: 714–721, 1981.PubMedGoogle Scholar
  5. 5.
    Suttorp N, Simon L: Lung cell oxidant injury. Enhancement of polymorphonuclear leukocyte mediated cytotoxicity in lung cells exposed to sustained in vitro hyporoxia. J Clin Invest 70:342– 350, 1982.PubMedGoogle Scholar
  6. 6.
    Martin WJ II: Neutrophils kill pulmonary endothelial cells by a hydrogen peroxide-dependent pathway. An in vitro model of neutrophil-mediated lung injury. Ann Rev RespirDis 130: 209–213, 1984.Google Scholar
  7. 7.
    Varani G, Fligiel SEG, Till OG, et at: Pulmonary endothelial cell killing by human neutrophils. Possible involvement of hydroxyl radical. Lab Invest 53: 656–663, 1985.PubMedGoogle Scholar
  8. 8.
    Harlan JM, Killen PD, Harker LA, et al: Neutrophil-mediated endothelial injury in vitro. Mecha-nisms of cell detachment. J Clin Invest 68: 1394–1403, 1981.PubMedGoogle Scholar
  9. 9.
    Harlan JM, Levine JD, Callahan KS, et al: Glutathione redox cycle protects cultured endothelial cells against lysis by extracellularly generated hydrogen peroxide. J Clin Invest 73: 706–713, 1984.PubMedGoogle Scholar
  10. 10.
    Andreoli SP, Baehner RL, Bergstein JM: In vitro detection of endothelial cell damage using 2- deoxy-D-3H-glucose: Comparison with chromium-51, 3H-leucine, 3H-adenine, and lactate dehy-drogenase. J Lab Clin Med 106: 253–261, 1985.PubMedGoogle Scholar
  11. 11.
    Hoover RL, Robinson JM, Karnovsky MJ: Superoxide production by polymorphonuclear leuko-cytes is inhibited by contact with endothelial cells. J Cell Biol 95: 37A, 1982.Google Scholar
  12. 12.
    Cronstein BN, Levin RI, Belanoff J, et al: Adenosine: An endogenous inhibitor of neutrophil- mediated injury to endothelial cells. J Clin Invest 78: 760–770, 1986.PubMedGoogle Scholar
  13. 13.
    Diener AM, Beatty PG, Ochs HD, et al: The role of neutrophil membrane glycoprotein 150 (GP-150) in neutrophil-mediated endothelial cell injury in vitro. J Immunol 135: 537–543, 1985.PubMedGoogle Scholar
  14. 14.
    Smedly LA, Tonnesen MG, Sandhaus RA, et al: Neutrophil-mediated injury to endothelial cells. Enhancement by endotoxin and essential role of neutrophil elastase. J Clin Invest 77: 1233–1243, 1986.PubMedGoogle Scholar
  15. 15.
    Fehr J, Moser R, Leppert D, et al: Antiadhesive properties of biological surfaces are protective against stimulated granulocytes. J Clin Invest 76: 535–542, 1985.PubMedGoogle Scholar
  16. 16.
    Dobrina A, Patriarca P: Neutrophil-endothelial cell interaction. Evidence for and mechanism of the self protection of bovine microvascular endothelial cells from hydrogen peroxide-induced oxidative stress. J Clin Invest 78: 462–471, 1986.PubMedGoogle Scholar
  17. 17.
    Whorton AR, Montgomery ME, Kent RS: Effect of hydrogen peroxide on prostaglandin production and cellular integrity in cultured porcine aortic endothelial cells. J Cell Invest 76: 295–302, 1985.Google Scholar
  18. 18.
    Ager A, Gordon JL: Differential effects of hydrogen peroxide on indices of endothelial cell function. J Exp Med 159: 592–603, 1984.PubMedGoogle Scholar
  19. 19.
    Spragg RG, Hinshaw DB, Hyslop PA, et al: Alterations in adenosine triphosphate and energy charge in cultured endothelial and P388Ü! cells after oxidant injury. J Clin Invest 76: 1471–1476, 1985.PubMedGoogle Scholar
  20. 20.
    Guthrie LA, McPhail LC, Henson PM, et al: The priming of neutrophils for enhanced release of oxygen metabolites by bacterial lypopolysaccharide: evidence for increased activity of the superoxide producing enzyme. J Exp Med 160: 1656–1671, 1984.PubMedGoogle Scholar
  21. 21.
    Rossi F: The Of forming NADPH oxidase of the phagocytes. Nature, mechanisms of activation and function. Biochim Biophys Acta 853: 65–89, 1986.PubMedGoogle Scholar
  22. 22.
    Shasby DM, Vanbenthuysen KM, Tate RM, et al: Granulocytes mediate acute edematous lung injury in rabbits and in isolated rabbit lungs perfused with phorbol myristate acetate: Role of oxygen radicals. Am Rev Respir Dis 125: 443–447, 1982.PubMedGoogle Scholar
  23. 23.
    Tate RM, Van Benthuysen KM, Shasby DM, et al: Dimethylthiourea, a hydroxyl radical scav-enger, blocks oxygen radical-induced acute edematous lung injury in an isolated perfused lung. Am Rev Respir Dis 123:243, 1981 (abst).Google Scholar
  24. 24.
    Craddock PR, Fehr J, Brigham KL, et al: Complement and leukocyte-mediated pulmonary dys-function in hemodialysis. N Engl J Med 296: 769–774, 1977.PubMedGoogle Scholar
  25. 25.
    Craddock PR, Fehr J, Dalmasso AP, et al: Hemodialysis leukopenia. Pulmonary vascular leuko- stasis resulting from complement activation by dialyzer cellophane membranes. J Clin Invest 59: 879–888, 1977.PubMedGoogle Scholar
  26. 26.
    O’Faherty JT, Craddock PR, Jacob HS: Effect of intravascular complement activation on gran-ulocyte adhesiveness and distribution. Blood 51: 731–739, 1978.Google Scholar
  27. 27.
    Hohn DC, Meyers AJ, Gherini ST, et al: Production of acute pulmonary injury by leukocytes and activated complement. Surgery 88: 48–58, 1980.PubMedGoogle Scholar
  28. 28.
    Hammerschmidt DE, Harris PD, Wayland JH, et al: Complement-induced granulocyte aggregation in vivo. Am J Pathol 102: 146–150, 1981.PubMedGoogle Scholar
  29. 29.
    Henson PM, Larsen GL, Webster RO, et al: Pulmonary microvascular alterations and injury induced by complement fragments: Synergistic effect of complement activation, neutrophil se-questration and prostaglandins. Ann NY Acad Sei 384: 287–300, 1982.Google Scholar
  30. 30.
    Gee MH, Perkowski SZ, Havill AM, et al: Role of prostaglandins and leukotrienes in complement- initiated lung vascular injury. Chest 83: 82–85, 1983.Google Scholar
  31. 31.
    Perkowski SZ, Havill AM, Flynn J, et al: Role of intrapulmonary release of eicosanoids and superoxide anion as mediators of pulmonary dysfunction and endothelial injury in sheep with intermittent complement activation. Circ Res 53: 574–583, 1983.PubMedGoogle Scholar
  32. 32.
    Meyrick BO, Brigham KL: The effect of a single infusion of zymosan-activated plasma on the pulmonary microcirculation of sheep. Structure-function relationships. Am J Pathol 114: 32–45, 1984.PubMedGoogle Scholar
  33. 33.
    Meyrick BO: Endotoxin-mediated pulmonary endothelial cell injury. Fed Proc 45: 19–24, 1986.PubMedGoogle Scholar
  34. 34.
    Webster RO, Larsen GL, Henson PM: Lack of inflammatory effects on the rabbit lung of intra-vascular complement activation. Fed Proc 40:767, 1981 (abst).Google Scholar
  35. 35.
    Till GO, Johnson KJ, Kunkel R, et al: Intravascular activation of complement and acute lung injury. Dependency on neutrophils and toxic oxygen metabolites. J Clin Invest 69: 1126–1135, 1982.PubMedGoogle Scholar
  36. 36.
    Ward PA, Till GO, Kunkel R, et al: Evidence for role of hydroxyl radical in complement and neutrophil-dependent tissue injury. J Clin Invest 72: 789–801, 1983.PubMedGoogle Scholar
  37. 37.
    Till GO, Beauchamp C, Menapace D, et al: Oxygen radical dependent lung damage following thermal injury to rat skin. J Trauma 28: 269–277, 1983.Google Scholar
  38. 38.
    Till GO, Ward PA: Systemic complement activation and acute lung injury. Fed Proc 45: 13–18, 1986.PubMedGoogle Scholar
  39. 39.
    Brigham KL, Woolverton WC, Blake LH, et al: Increased sheep lung vascular permeability caused by Pseudomonas bacteremia. J Clin Invest 54: 792–804, 1974.PubMedGoogle Scholar
  40. 40.
    Heflin AC, Brigham KL: Prevention by granulocyte depletion of increased vascular permeability of sheep lung following endotoxemia. J Clin Invest 68: 1253–1260, 1981.PubMedGoogle Scholar
  41. 41.
    Meyrick B, Brigham KL: Acute effects of Escherichia coli endotoxin on the pulmonary microcir-culation of anesthetized sheep. Structure-function relationships. Lab Invest 48: 458–470, 1983.PubMedGoogle Scholar
  42. 42.
    Worthen GS, Haslett C, Smedly LA, et al: Lung vascular injury induced by chemotactic factors: enhancement by bacterial endotoxins. Fed Proc 45: 7–12, 1986.PubMedGoogle Scholar
  43. 43.
    Garcia-Szabo RR, Johnson A, Malik AB: Leukocytes are required for the trypsin-induced increase in lung vascular permeability. Am J Pathol 124: 377–383, 1986.PubMedGoogle Scholar
  44. 44.
    Judges D, Sherkey P, Cheung H, et al: Pulmonary microvascular fluid flux in a large animal model of sepsis: Evidence for increased pulmonary endothelial permeability accompanying surgically induced peritonitis in sheep. Surgery 99: 222–234, 1986.PubMedGoogle Scholar
  45. 45.
    Shaw JO, Henson PM: Pulmonary intravascular sequestration of activated neutrophils. Failure to induce light-microscopic evidence of lung injury in rabbits. Am J Pathol 108: 17–23, 1982.PubMedGoogle Scholar
  46. 46.
    Fridovich I: The biology of oxygen radicals. Science 201: 875–880, 1978.PubMedGoogle Scholar
  47. 47.
    Weiss SJ, Lo Buglio AF: Biology of disease. Phagocyte-generated oxygen metabolites and cellular injury. Lab Invest 47: 5–18, 1982.PubMedGoogle Scholar
  48. 48.
    Fantone JC, Ward PA: Role of oxygen-derived free radicals and metabolites in leukocyte-depen-dent inflammatory reactions. J Pathol 107: 397–418, 1982.Google Scholar
  49. 49.
    Freeman BA, Crapo JD: Biology of disease. Free radicals and tissue injury. Lab Invest 47:412– 426, 1982.Google Scholar
  50. 50.
    Greenwald RA, Moy WW, Lazarus D: Degradation of cartilage proteoglycans and collagen by superoxide radical. Arthritis Rheum 19:799, 1976 (abst).Google Scholar
  51. 51.
    Greenwald RA, Moy WW: Effect of oxygen-derived free radicals on hyaluronic acid. Arthritis Rheum 23: 455–463, 1980.PubMedGoogle Scholar
  52. 52.
    Klebanoff SJ, Clark RA (eds): The Neutrophil: Function and Clinical Disorders. Amsterdam, Elsevier/ North-Holland, 1978.Google Scholar
  53. 53.
    Senior RM, Campbell EJ: Neutral proteinases from human inflammatory cells. A critical review of their role in extracellular matrix degradation, in Ward PA (ed): Clinics in Laboratory Medicine. Philadelphia, WB Saunders, 1983, vol 3: Symposium on Tissue Immunopathology, p 645.Google Scholar
  54. 54.
    Fritz H, Jochum M, Duswald KH, et al: Granulocyte proteinases as mediators of unspecific proteolysis in inflammation: A review, in Goldberg DM, Werner M (eds): Selected Topics in Clinical Enzymology, Berlin, de Gruyter, 1984 vol 2, p 305.Google Scholar
  55. 55.
    McDonald JA, Kelley DG: Degradation of fibronectin by human leukocyte elastase. Release of biologically-active fragments. J Biol Chem 255: 8848–8858, 1980.PubMedGoogle Scholar
  56. 56.
    Gadek JE, Fells JA, Wright DG, et al: Human neutrophil elastase functions as a type III collagen “collagenase.” Biochem Biophys Res Commun 95: 1815–1822, 1980.Google Scholar
  57. 57.
    Mainardi CL, Dixit SN, Kang AH: Degradation of type IV (basement membrane) collagen by a proteinase isolated from human polymorphonuclear leukocyte granules. J Biol Chem 255:5435– 5441, 1980.Google Scholar
  58. 58.
    Weiss SJ, Regiani S: Neutrophils degrade subendothelial matrices in the presence of alpha-1- proteinase inhibitor. Cooperative use of lysosomal proteinases and oxygen metabolites. J Clin Invest 73: 1297–1303, 1984.PubMedGoogle Scholar
  59. 59.
    Le Roy EC, Ager A, Gordon JL: Effects of neutrophil elastase and other proteases on porcine aortic endothelial prostaglandin I2 production, adenine nucleotide release, and responses to vasoactive agents. J Clin Invest 74: 1003–1010, 1984.Google Scholar
  60. 60.
    Ohlsson K: Interaction of granulocyte neutral proteases with alphaj-antitrypsin, alpha2-mac- roglobulin and alphaj–antichymotrypsin, in: Havemann K, Janoff A (eds): Neutral Proteases of Human Polymorphonuclear leukocytes. Baltimore, Urban & Schwarzenberg, 1978, p 167.Google Scholar
  61. 61.
    Travis J, Giles PJ, Porcelli L, et al: Human leukocyte elastase and cathepsin G: Structural and functional characteristics. Ciba Found Symp 75: 51–68, 1980.Google Scholar
  62. 62.
    Weiss SJ: Oxygen as a weapon in the phagocyte armamentarium, in Ward PA (ed): Handbook of Inflammation: Immunology of Inflammation, Amsterdam, Elsevier, 1983, vol 4, p 37.Google Scholar
  63. 63.
    Banda MJ, Clark EJ, Werb Z: Regulation of alphav-proteinase inhibitor function by rabbit alveolar macrophages. J Clin Invest 75: 1758–1762, 1985.PubMedGoogle Scholar
  64. 64.
    Johnson KJ, Varani J: Substrate hydrolysis by immune complex-activated neutrophils: Effect of physical presentation of complexes and protease inhibitors. J Immunol 127: 1875–1879, 1981.PubMedGoogle Scholar
  65. 65.
    Campbell EJ, Senior RM, McDonald JA, et al: Proteolysis by neutrophils. Relative importance of cell-substrate contact and oxidative inactivation of proteinase inhibitors in vitro. J Clin Invest 70: 845–852, 1982.PubMedGoogle Scholar
  66. 66.
    Carp H, Janoff A: In vitro suppression of serum elastase-inhibitory capacity by reactive oxygen species generated by phagocytosing polymorphonuclear leukocytes. J Clin Invest 63: 793–797, 1979.PubMedGoogle Scholar
  67. 67.
    Carp H, Janoff A: Phagocyte-derived oxidants suppress the elastase-inhibitory capacity of alpha r proteinase inhibitor in vitro. J Clin Invest 66: 987–995, 1980.PubMedGoogle Scholar
  68. 68.
    Zaslow MC, Clark RA, Stone PJ, et al: Human neutrophil elastase does not bind to alphav-protease inhibitor that has been exposed to activated human neutrophils. Am Rev Respir Dis 128: 434–439, 1983.PubMedGoogle Scholar
  69. 69.
    Fligiel SEG, Lee EC, McCoy, JP, et al: Protein degradation following treatment with hydrogen peroxide. Am J Pathol 115: 418–425, 1984.PubMedGoogle Scholar
  70. 70.
    Pearson JD, Gordon JL: Vascular endothelial and smooth muscle cells in culture selectively release adenine nucleotides. Nature (Lond) 281: 384–386, 1979.Google Scholar
  71. 71.
    Cronstein BN, Kramer SB, Weismann G, et al: Adenosine: A physiological modulator of superox-ide anion generation by human neutrophils. J Exp Med 158: 1160–1177, 1983.PubMedGoogle Scholar
  72. 72.
    Roberts PA, Newby AC, Hallet MB, et al: Inhibition by adenosine of reactive oxigen metabolite production by human polymorphonuclear leukocytes. Biochem J 227: 669–674, 1985.PubMedGoogle Scholar
  73. 73.
    Cronstein BN, Rosenstein ED, Kramer SB, et al: Adenosine: A physiologic modulator of superox-ide anion generation by human neutrophils. Adenosine acts via an A2 receptor on human neu-trophils. J Immunol 135: 1366–1371, 1985.PubMedGoogle Scholar
  74. 74.
    Hirschhorn RV, Roegner-Maniscalco V, Kuritsky L, et al: Bone marrow transplanation only partially restores purine metabolites to normal in adenosine deaminase deficient patients. J Clin Invest 68: 1387–1393, 1981.PubMedGoogle Scholar
  75. 75.
    Ody C, Bach-Dieterle Y, Wand I, et al: Effect of hyperoxia on superoxide dismutase content of pig pulmonary artery and aortic endothelial cells in culture. Exp Lung Res 1: 271–279, 1980.Google Scholar
  76. 76.
    Marklund SL, Westman NG, Lundgren E, et al: Copper- and zinc-containing superoxide dis-mutase, catalase, and glutathione peroxidase in normal and neoplastic human cell lines and normal human tissues. Cancer Res 42: 1955–1961, 1982.PubMedGoogle Scholar
  77. 77.
    Shingu M, Yoshioka K, Nobunaga M, et al: Human vascular smooth muscle cells and endothelial cells lack catalase activity and are susceptible to hydrogen peroxide. Inflammation 9: 309–320, 1985.PubMedGoogle Scholar
  78. 78.
    Marklund SL: Physiological aspects of extracellular superoxide dismutase, in Rotilio G (ed): Superoxide and Superoxide Dismutase in Chemistry, Biology and Medicine. Amsterdam, Elsevier, 1986, p 438.Google Scholar
  79. 79.
    Housset B, Junod AF: Effects of culture conditions and hyperoxia on antioxidant enzymes in pig pulmonary artery and aortic endothelium. Biochim Biophys Acta 716: 283–289, 1982.PubMedGoogle Scholar
  80. 80.
    Tsan MF, Danis EH, Del Vecchio PJ, et al: Enhancement of intracellular glutathione protects endothelial cells against peroxidative damage. Biochem Biophys Res Commun 127: 270–276, 1985.PubMedGoogle Scholar
  81. 81.
    Dobrina A, Bulli G, Cecovini G, et al: Patterns of H202 degradation in bovine and human vascular endothelial cell, in Mauri C, Rizzo SC, Ricevuti G (eds): The Biology of Phagocytes in Health and Disease. Advances in Bioscience. Oxford, Pergamon, 1987, p 155.Google Scholar
  82. 82.
    Fehr J, Jacob HS: In vitro granulocyte adherence and in vivo margination: Two associated comple- ment-dependent functions. Studies based on the acute neutropenia of filtration leukophoresis. J Exp Med 146: 641–652, 1977.PubMedGoogle Scholar
  83. 83.
    Meyrick B, Hoffman LH, Brigham KL: Chemotaxis of granulocytes across bovine pulmonary artery intimal explants without endothelial cell injury. Tissue Cell 16: 1–16, 1984.PubMedGoogle Scholar
  84. 84.
    Huang AG, Furie MB, Silverstein SC: Human neutrophil migration does not alter electrical resistance across cultured human endothelial cell monolayers, in Fourth International Symposium on the Biology of the Vascular Endothelial Cell, August 19–23, 1986, Noordwijkerhout, The Netherlands, p 20 (abst).Google Scholar
  85. 85.
    Shaw JO, Henson PM, Henson J, et al: Lung inflammation induced by complement-derived chemotactic fragments in the alveolus. Lab Invest 42: 547–558, 1980.PubMedGoogle Scholar
  86. 86.
    Schleimer RP, Rutledge BK: Cultured human vascular endothelial cells acquire adhesiveness for neutrophils after stimulation with interleukin 1, endotoxin and tumor-promoting phorbol diesters. J Immunol 136: 649–654, 1986.PubMedGoogle Scholar
  87. 87.
    Kirkpatrick CJ, Melzner I: Alterations in the biophysical properties of the human endothelial cell plasma membrane induced by a chemotactic tripeptide: Correlation with enhanced adherence of granulocytes. J Pathol 144: 201–211, 1984.PubMedGoogle Scholar
  88. 88.
    Zimmermann GA, Hill HR: Inflammatory mediators stimulate granulocyte adherence to cultured human endothelial cells. Thromb Res 35: 203–217, 1984.Google Scholar
  89. 89.
    Bevilacqua MP, Pober JS, Wheeler ME, et al: Interleukin 1 acts on cultured human vascular endothelium to increase the adhesion of polymorphonuclear leukocytes, monocytes and related leukocyte cell lines. J Clin Invest 76: 2003–2011, 1985.PubMedGoogle Scholar
  90. 90.
    Bevilacqua MP, Pober JS, Wheeler ME, et al: Interleukin 1 activation of vascular endothelium. Effects of proagulant activity and leukocyte adhesion. Am J Pathol 121: 393–403, 1985.Google Scholar
  91. 91.
    Gamble JR, Harlan JM, Klebanoff SJ, et al: Stimulation of the adherence of neutrophils to umbilical vein endothelium by human recombinant tumor necrosis factor. Proc Natl Acad Sei USA 82: 8667–8671, 1985.Google Scholar
  92. 92.
    Mclntyre TM, Zimmermann GA, Prescott SM: Leukotrienes C4 and D4 stimulate human endothelial cells to synthesize platelet-activating factor and bind neutrophils. Proc Natl Acad Sei USA 83: 2204–2208, 1986.Google Scholar
  93. 93.
    Prescott SM, Zimmermann GA, Mclntyre TM: Human endothelial cells in culture produce platelet- activating factor (l-alkyl-2-acetyl-stt-glycero-3-phosphocholine) when stimulated with thrombin. Proc Natl Acad Sei USA 81: 3534–3538, 1984.Google Scholar
  94. 94.
    Zimmermann GA, Mclntyre TM, Prescott SM: Thrombin stimulates the adherence of neutrophils to human endothelial cells in vitro. J Clin Invest 76: 2235–2246, 1985.Google Scholar
  95. 95.
    Shaw JO, Pinckard RN, Ferrigni KS, et al: Activation of human neutrophils with 1-O-hex- adecyl/octadecyl-2-acetyl-5-glyceryl-3-phosphorylcholine (PAF). J Immunol 127: 1250–1255, 1981.PubMedGoogle Scholar
  96. 96.
    Ryan US, Schultz DR, Ryan JW: Fe and C3b receptors on pulmonary endothelial cells; induction by injury. Science 214: 557–559, 1981.PubMedGoogle Scholar
  97. 97.
    Ryan US: The endothelial surface and response to injury. Fed Proc 45: 101–108, 1986.PubMedGoogle Scholar
  98. 98.
    Niva Y, Shomija K: Enhanced neutrophilic functions in mucocutaneous lymph node syndrome, with special reference to the possible role of increased oxygen intermediate generation in the pathogenesis of coronary thromboarthritis. J Pediatr 104: 56–60, 1984.Google Scholar
  99. 99.
    Somiya K, Niva Y, Shimoda K, et al: Treatment with liposomal superoxide dismutase of patients with Kawasaki disease, in Rotilio G (ed): Superoxide and Superoxide Dismutase in Chemistry, Biology and Medicine. Amsterdam, Elsevier, 1986, p 513.Google Scholar
  100. 100.
    Leung DYM, Collins T, Lapierre LA, et al: Immunoglobulin M antibodies present in the acute phase of Kawasaki syndrome lyse cultured vascular endothelial cells stimulated by gamma inter-feron. J Clin Invest 77: 1428–1435, 1986.PubMedGoogle Scholar
  101. 101.
    Cines DB, Lyss AP, Reeher M, et al: Presence of complement fixing anti-endothelial cell anti-bodies in systemic lupus erythematosus. J Clin Invest 73: 611–625, 1984.PubMedGoogle Scholar
  102. 102.
    Paul LC, van Es LA, Balwinn WM III: Antigens in human renal allografts. Clin Immunol Immu- nopathol 19: 206–223, 1981.Google Scholar
  103. 103.
    McCord JM: Oxygen-derived free radicals postischemic tissue injury. N Engl J Med 312: 159–163, 1985.PubMedGoogle Scholar
  104. 104.
    Hearse DJ: Reperfusion of the ischemic myocardium. Clin Res Rev 4: 58–61, 1984.Google Scholar
  105. 105.
    Jarasch ED, Grund C, Bruder G, et al: Localization of xanthine oxidase in mammary gland epithelium and capillary endothelium. Cell 25: 67–82, 1981.PubMedGoogle Scholar
  106. 106.
    Del Maestro RF, Thaw HH, Björk J, et al: Free radicals as mediators of tissue injury. Acta Physiol Scand (suppl) 492: 43–57, 1980.Google Scholar
  107. 107.
    Engler RL, Schmid-Schönbein GW, Pavelec RS: Leukocyte capillary plugging in myocardial ischemia and reperfusion in the dog. Am J Pathol 111: 98–111, 1983.PubMedGoogle Scholar
  108. 108.
    Romson J, Hook B, Kunkel S, et al: Reduction in the extent of myocardial ischemic injury by neutrophil depletion in the dog. Circulation 67: 1016–1023, 1983.PubMedGoogle Scholar
  109. 109.
    Groegaard B, Schuerer L, Gerdin B, et al: Involvement of neutrophils in the cortical blood flow impairment after cerebral ischemia in rat; effects of antineutrophil serum and superoxide dis-mutase, in Rotilio G (ed): Superoxide and Superoxide Dismutase in Chemistry, Biology and Medicine. Amsterdam, Elsevier, 1986, p 608.Google Scholar
  110. 110.
    Hammerschmidt DE: Activation of the complement system and of granulocytes in lung injury: The adult respiratory distress syndrome. Adv Inflammation Res 5: 147–172, 1983.Google Scholar
  111. 111.
    Cochrane CG, Aikin BS: Polymorphonuclear leukocytes in immunologic reactions. The destruction of vascular basement membrane in vivo and in vitro. J Exp Med 124: 733–752, 1966.PubMedGoogle Scholar
  112. 112.
    DeShazo CV, Henson PM, Cochrane CG: Acute immunologic arthritis in rabbits. J Clin Invest 51: 50–57, 1972.PubMedGoogle Scholar
  113. 113.
    Johnson KJ, Ward PA: Acute immunologic pulmonary alveolitis. J Clin Invest 54: 349–357, 1974.PubMedGoogle Scholar
  114. 114.
    Fligiel SEG, Ward PA, Johnson KJ, et al: Evidence for a role of hydroxyl radical in immune- complex-induced vasculitis. Am J Pathol 115: 375–382, 1984.PubMedGoogle Scholar
  115. 115.
    Hawkins D, Cochrane CG: Glomerular basement membrane damage in immunological glomer-ulonephritis. Immunology 14: 665–681, 1968.PubMedGoogle Scholar
  116. 116.
    Ward PA, Hill JH: Biologic role of complement products. Complement-derived leukotactic activity extractable from lesions of immunologic vasculitis. J Immunol 108: 1137–1145, 1972.PubMedGoogle Scholar
  117. 117.
    Humphrey JH: The mechanisms of Arthus reactions. I. The role of polymorphonuclear leukocytes and other factors in reversed passive Arthus reactions in rabbits. Br J Exp Pathol 36: 268–282, 1955.PubMedGoogle Scholar
  118. 118.
    Cochrane CG, Weigle WO, Dixon FJ: The role of polymorphonuclear leukocytes in the initiation and cessation of the Arthus vasculitis. J Exp Med 110: 481–494, 1959.PubMedGoogle Scholar
  119. 119.
    Ward PA, Cochrane CG: Bound complement and immunologic injury of blood vessels. J Exp Med 121: 215–234, 1965.PubMedGoogle Scholar
  120. 120.
    Johnson KJ, Ward PA: Role of oxygen metabolites in immune complex injury of lung. J Immunol 126: 2365–2369, 1981.PubMedGoogle Scholar
  121. 121.
    Rinaldo EJ, Rogers RM: Adult respiratory distress syndrome: Changing concepts of lung injury and repair. N Engl J Med 306: 900–909, 1982.PubMedGoogle Scholar
  122. 122.
    Fowler AA, Hamman RF, Good JT, et al: The respiratory distress syndrome: Risk with common predisposition. Ann Intern Med 98: 593–597, 1983.PubMedGoogle Scholar
  123. 123.
    Hyers TM, Fowler AA: Adult respiratory distress syndrome: Causes, morbidity and mortality. Fed Proc 45: 25–29, 1986.PubMedGoogle Scholar
  124. 124.
    Pepe PE, Potkin RT, Reus DH, et al: Clinical indicators of the adult respiratory distress syndrome. Am J Surg 144: 124–130, 1982.PubMedGoogle Scholar
  125. 125.
    Weigelt JA, Snyder WH III, Mitchell RA: Early identification of patients prone to develop adult respiratory distress syndrome. Am J Surg 142: 687–691, 1981.PubMedGoogle Scholar
  126. 126.
    Levin J, Poore TE, Zauber NP, et al: Detection of endotoxin in the blood of patients with sepsis due to gram negative bacteria. N Engl J Med 283: 1313–1316, 1970.PubMedGoogle Scholar
  127. 127.
    Goldstein IM, Cala D, Radin A, et al: Evidence of complement catabolism in acute pancreatitis. Am J Med Sei 275: 257–264, 1978.Google Scholar
  128. 128.
    Morrison DC, Kline LF: Activation of the classical and properdin pathways of complement by bacterial lipopolysaccharides (LPS). J Immunol 118: 362–368, 1977.PubMedGoogle Scholar
  129. 129.
    Hammerschmidt DE, Weaver LJ, Hudson LD, et al: Association of complement activation and elevated plasma-C5a with adult respiratory distress syndrome: Pathophysiological relevance and possible prognostic value. Lancet 1: 947–949, 1980.PubMedGoogle Scholar
  130. 130.
    Weinberg PF, Matthay MA, Webster RO, et al: Lack of relationship between complement activation and acute lung injury. Am Rev Respir Dis 127:95, 1983 (abst).Google Scholar
  131. 131.
    Spitzer RE, Vallota EH, Forrestal J, et al: Serum C3 lytic system in patients with glomerulonephritis. Science 164: 436–437, 1969.PubMedGoogle Scholar
  132. 132.
    McGuire WW, Spragg RG, Cohen AB, et al: Studies on the pathogenesis of the adult respiratory distress syndrome. J Clin Invest 69: 543–553, 1982.PubMedGoogle Scholar
  133. 133.
    Zimmerman GA, Renzetti AD, Hill HR: Functional and metabolic activity of granulocytes from patients with adult respiratory distress syndrome: Evidence for activated neutrophils in the pulmo-nary circulation. Am Rev Respir Dis 127: 290–300, 1983.PubMedGoogle Scholar
  134. 134.
    Fowler AA, Fisher BJ, Centor RM, Et Al: Development of the adult respiratory distress syndrome: progressive alteration of neutrophil chemotactic and secretory processes. Am J Pathol 116:427– 435, 1984.Google Scholar
  135. 135.
    Lee CT, Fein AM, Lippman M, et al: Elastolytic activity in pulmonary lavage fluid from patients with adult respiratory distress syndrome. N Engl J Med 304: 192–196, 1981.PubMedGoogle Scholar
  136. 136.
    Worthen GS, Henson PM: Mechanisms of acute lung injury, in Ward PA (Ed): ry Medicine, Philadelphia, WB Saunders, 1983, vol 3: Symposium on Tissue Immunopathology, p 601.Google Scholar
  137. 137.
    Jacob HS, Goldstein IM, Shapiro I, et al: Sudden blindness in acute pancreatitis: Possible manifestation of complement-induced retinal leukostasis. Arch Intern Med 141: 134–136, 1981.PubMedGoogle Scholar
  138. 138.
    Kawasaki T: Acute febrile mucocutaneous syndrome with lymphoid involvement with specific desquamation of the fingers and toes in children: clinical observations of 50 cases. Jpn J Allerg 16: 178–222, 1967.Google Scholar
  139. 139.
    Hirose S, Hamashima Y: Morphological observations on the vasculitis in the mucocutaneous lymph node syndrome. Eur J Pediatr 129: 17–27, 1978.PubMedGoogle Scholar
  140. 140.
    Landing BH, Larson JE: Are infantile periarteritis nodosa and fatal mucocutaneous lymph node syndrome the same? Pediatrics 59: 651–662, 1977.PubMedGoogle Scholar
  141. 141.
    Kawasaki T: Acute febrile mucocutaneous lymph node syndrome and sudden death. Acta Pediatr Jpn 75: 433–434, 1971.Google Scholar
  142. 142.
    Kato H, Koike S, Yamamoto M, et al: Coronary aneurisms in infants and young children with acute febrile mucocutaneous lymph node syndrome. J Pediatr 86: 892–898, 1975.PubMedGoogle Scholar
  143. 143.
    Bulkley GB, Morris JB: Role of oxygen derived free radicals as mediators of post-ischemic injury: A clinically oriented overview, in Rotilio G (ed): Superoxide and Superoxide Dismutase in Chemistry, Biology and Medicine. Amsterdam, Elsevier, 1986, p 565.Google Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • Aldo Dobrina
    • 1
  • Pierluigi Patriarca
    • 1
  1. 1.Institute of General PathologyUniversity of TriesteTriesteItaly

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