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Deleterious effects of endotoxin on cultured endothelial cells: An in vitro model of vascular injury

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The effects of endotoxin-triggered granulocytes on the viability of endothelial cells in vitro was investigated. Endotoxin or its lipid A component caused granulocytes to adhere to and significantly damage cultured endothelial cells. Fresh serum is not necessary but does amplify both adherence and endothelial injury. Much of the endothelial injury was inhibited by free-radical scavengers or by blocking granulocyte adhesion to endothelial cells and appears to result from free radical production by the stimulated granulocyte. Studies in this model suggest a pathogenic role for the endotoxin-triggered granulocyte in the Shwartzman reaction and perhaps related clinical disorders.

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References

  1. Sandritter, W. C., C. M. Hermayer, U. N. Riede, N. Freudenberg, andH. Grimm. 1978. The shock lung syndrome (an overview).Pathol. Res. Pract. 162:7–23.

    Google Scholar 

  2. Schweinburg, F. B., R. G. Smiddy, andJ. Fine. 1959. The granulocytopenic response in hemorrhagic shock.J. Clin. Invest. 38:673–679.

    Google Scholar 

  3. Elin, R. J., andS. M. Wolff. 1976. Biology of endotoxin.Ann. Rev. Med. 27:127–141.

    Google Scholar 

  4. Shwartzman, G., P. Klemperer, andI. E. Gerber. 1936. The phenomenon of local tissue reactivity to bacterial filtrates.J. Am. Med. Assoc. 107:1946–1951.

    Google Scholar 

  5. Good, R. A., andL. Thomas. 1953. Studies on the generalized Shwartzman reaction. IV. Prevention of the local and generalized Shwartzman reaction with heparin.J. Exp. Med. 97:871–881.

    Google Scholar 

  6. Levin, J., andE. Beck. 1966. A reappraisal of the role of blood coagulation and platelets in the generalized Shwartzman phenomenon.Thrombos. Diathes. Haemorrh. 15:519–522.

    Google Scholar 

  7. Gaynor, E., C. Bouvier, andT. H. Spaet. 1970. Vascular lesions: Possible pathogenetic basis of the generalized Shwartzman reaction.Science 170:986–988.

    Google Scholar 

  8. Horn, R. G. 1973. Evidence for participation of granulocytes in the pathogenesis of the generalized Shwartzman reaction: A review.J. Infect. Dis. 128:134–143.

    Google Scholar 

  9. Stetson, C. A., andR. A. Good. 1951. Studies on the generalized Shwartzman reaction. Evidence for the participation of PMNs in the phenomenon.J. Exp. Med. 93:49–51.

    Google Scholar 

  10. Sacks, T., C. F. Moldow, C. R. Craddock, T. K. Bowers, andH. S. Jacob. 1978. Oxygen radicals mediate endothelial cell damage by complement-stimulated granulocytes.J. Clin. Invest. 61:1161–1167.

    Google Scholar 

  11. Jaffe, E. A., L. W. Hoyer, andR. L. Nachman. 1973. Synthesis of antihemophilic factor antigens by cultured human endothelial cells.J. Clin. Invest. 52:2757–2764.

    Google Scholar 

  12. Jaffe, E. A., R. L. Nachman, C. G. Becker, andC. R. Minick. 1973. Culture of human endothelial cells derived from umbilical veins.J. Clin. Invest. 52:2745–2756.

    Google Scholar 

  13. Boyum, A. 1968. Isolation of mononuclear cells and granulocytes from human blood. Isolation of mononuclear cells by one centrifugation; and granulocytes by combining centrifugation and sedimentation at lg.Scand. J. Clin. Lab. Invest. 21 (Suppl. 97):77–89.

    Google Scholar 

  14. Galanos, C., E. T. Rietschel, O. Lüderitz, andO. Westphal. 1971. Interaction of lipopolysaccharide and lipid A with complement.Eur. J. Biochem. 19:143–152.

    Google Scholar 

  15. Galanos, C., E. T. Rietschel, O. Lüderitz, andO. Westphal. 1972. Biological activities of Lipid A complexed with bovine serum albumin.Eur. J. Biochem. 31:230–233.

    Google Scholar 

  16. Rickles, F. R., andP. D. Rick. 1977. Structural features ofSalmonella typhimurium lipopolysaccharides required for activation of tissue factor in human mononuclear cells.J. Clin. Invest. 59:1188–1195.

    Google Scholar 

  17. Celada, F., andB. Rotman. 1967. A fluorochromatic test for immunocytotoxicity against tumor cells and leukocytes in agarose plates.Proc. Natl. Acad. Sci. U.S.A. 57:630–636.

    Google Scholar 

  18. Rotman, B., andB. X. Papermaster. 1966. Membrane properties of living mammalian cells as studied by enzymatic hydroloysis of fluorogenic esters.Proc. Natl. Acad. Sci. U.S.A. 55:134–141.

    Google Scholar 

  19. Fehr, J., andH. S. Jacob. 1977.In vitro granulocyte adherence andin vivo margination: Two associated complement-dependent functions.J. Exp. Med. 146:641–652.

    Google Scholar 

  20. Goldstein, I. M., D. Ross, H. B. Kaplan, andG. Weissmann. 1975. Complement and immunoglobulins stimulate Superoxide production by human leukocytes independently of phagocytosis.J. Clin. Invest. 56:1155–1163.

    Google Scholar 

  21. Root, R. K., B. Metcalf, N. Ochino, andB. Chance. 1975. H2O2 release from human granulocytes during phagocytosis.J. Clin. Invest. 55:945–955.

    Google Scholar 

  22. Tsan, M., K. H. Douglass, andP. A. McIntyre. 1977. Hydrogen peroxide productions and killing of staphylococcus aureus by human polymorphonuclear leukocytes.Blood. 49:437–443.

    Google Scholar 

  23. Hammerschmidt, D. E., J. G. White, P. R. Craddock, andH. S. Jacob. 1979. Corticosteroids inhibit complement-induced granulocyte aggregation.J. Clin. Invest. 63:798–803.

    Google Scholar 

  24. Zigmond, S. M., andJ. G. Hirsch. 1972. Effects of cytochalasin B on polymorphonuclear leukocyte locomotion, phagocytosis, and glycolysis.Exp. Cell Res. 73:383–393.

    Google Scholar 

  25. Martz, E., S. J. Burakoff, andB. Benacerraf. 1974. Interruption of the sequential release of small and large molecules from tumor cells by low temperature during cytolysis mediated by immune T-cells or complement.Proc. Natl. Acad. Sci. U.S.A. 71:177–181.

    Google Scholar 

  26. Wall, R. T., J. M. Harlan, L. A. Harker, andG. E. Striker. 1977. Endotoxin mediated vascular injury.Blood 50: (suppl. 1):286.

    Google Scholar 

  27. Niemetz, J., andD. C. Morrison. 1977. Lipid A as the biologically active moiety in bacterial endotoxin (LPS)-initiated generation of procoagulant activity by peripheral blood leukocytes.Blood 49:947–956.

    Google Scholar 

  28. Galanos, C., O. Lüderitz, E. T. Rietschel, andO. Westphal. 1977. Newer aspects of the chemistry and biology of the bacterial lipopolysaccharides, with special reference to their lipid A component.Int. Rev. Biochem. 14:235–335.

    Google Scholar 

  29. Morrison, D. C., andL. F. Kline. 1977. Activation of the classical and properdin pathways of complement by bacterial lipopolysaccharides (LPS.).J. Immunol. 118:362–370.

    Google Scholar 

  30. Nowotny, A., U. H. Behling, andH. L. Chang. 1975. Relation of structure to function in bacterial endotoxins. VIII. Biological activities in a polysaccharide-rich fraction.J. Immunol.115:199–203.

    Google Scholar 

  31. Loos, M., D. Bitter-Suermann, andM. Dierich. 1974. Interaction of the first (C1), the second (C2), and the fourth (C4) component of complement with different preparations of bacterial lipopolysaccharides (LPS)J. Immunol. 112:935–944.

    Google Scholar 

  32. Morrison, D. C., andC. G. Cochrane. 1974. Direct evidence for Hagerman factor(factor XII) activation by bacterial lipopolysaccharides (endotoxins).J. Exp. Med. 140:797–806.

    Google Scholar 

  33. Doe, W. F., S. T. Yang, D. C. Morrison, S. J. Betz,andP. M. Henson. 1978. Macrophage stimulation by bacterial lipopolysaccharides.J. Exp. Med. 148:557–568.

    Google Scholar 

  34. Brigham, K. L., W. C. Woolverton, L. H. Blake, andN. C. Staub. 1974. Increased sheep lung vascular permeability caused by pseudomonas bacteremia.J. Clin. Invest. 54: 792–804.

    Google Scholar 

  35. Goldstein, I. M., D. Ross, G. Weissmann, andH. B. Kaplan. 1976. Influence of corticosteroids on human polymorphonuclear leukocyte function in vitro.Inflammation 1:305–315.

    Google Scholar 

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Yamada, O., Moldow, C.F., Sacks, T. et al. Deleterious effects of endotoxin on cultured endothelial cells: An in vitro model of vascular injury. Inflammation 5, 115–126 (1981). https://doi.org/10.1007/BF00914201

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