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. 1975 Dec 1;142(6):1570–1590. doi: 10.1084/jem.142.6.1570

Mediation systems in bacterial lipopolysaccharide-induced hypotension and disseminated intravascular coagulation. I. The role of complement

PMCID: PMC2190070  PMID: 1104750

Abstract

We have studied the role of complement in lipopolysaccharide (LPS)- induced hypotension and disseminated intravascular coagulation (DIC) by comparing the effects of injection of three preparations of LPS from E. Coli 0111:B4, S. minnesota Re595, and S. marcescens. Injections of nonlethal doses of these LPS preparations into normal rabbits produced decreases in mean arterial blood pressure during a 5-h period. When rabbits treated with cobra venom factor (CoF) to deplete C3 were injected with the various LPS preparations, mean arterial pressures fell at a rate and extent essentially identical to that observed in normal rabbits. Rabbits genetically deficient in C6 also demonstrated LPS-induced hypotensive changes. Only minimal, or no changes in plasma C3 levels or serum CH50 values were detected in normal rabbits after LPS injection. Hypotensive changes were also induced in rabbits when complement was rapidly activated by intravenous injection of CoF. In contrast to the hypotension induced by LPS, the fall in arterial pressure associated with the consumption of complement was short lived and required the rapid consumption of considerable amounts of C3. The occurrence of DIC noted in normal rabbits injected with each preparation of LPS was not inhibited in either rabbits treated with cobra factor or in C6-deficient rabbits. The DIC was most pronounced after injection of Re595 and S. marcescens LPS. Injection of the various LPS preparations produced a rapid disappearance of circulating neutrophils and mononuclear cells, which occurred with the same kinetics and to the same extent in normal, CoF-treated, and C6- deficient rabbits. Injection of either Re595 LPS or S. marcescens LPS produced a biphasic disappearance of circulating 51Cr-platelets. In contrast, injection of 0111:B4 LPS affected only slightly the rate of disappearance of 51Cr-platelets. Depletion of C3 by cobra factor treatment had no effect on the disappearance of platelets in animals injected with 0111:B4. In marked contrast cobra factor treatment greatly reduced the initial rapid disappearance of platelets in rabbits injected with either Re595 or S. marcescens LPS, but had no effect in the secondary disappearance phase.

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Selected References

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  1. ASTER R. H., JANDL J. H. PLATELET SEQUESTRATION IN MAN. I. METHODS. J Clin Invest. 1964 May;43:843–855. doi: 10.1172/JCI104970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Beller F. K. The role of endotoxin in disseminated intravascular coagulation. Thromb Diath Haemorrh Suppl. 1969;36:125–149. [PubMed] [Google Scholar]
  3. Benveniste J., Henson P. M., Cochrane C. G. Leukocyte-dependent histamine release from rabbit platelets. The role of IgE, basophils, and a platelet-activating factor. J Exp Med. 1972 Dec 1;136(6):1356–1377. doi: 10.1084/jem.136.6.1356. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cochrane C. G., Müller-Eberhard H. J., Aikin B. S. Depletion of plasma complement in vivo by a protein of cobra venom: its effect on various immunologic reactions. J Immunol. 1970 Jul;105(1):55–69. [PubMed] [Google Scholar]
  5. Corrigan J. J., Jr, Jordan C. M. Heparin therapy in septicemia with disseminated intravascular coagulation. N Engl J Med. 1970 Oct 8;283(15):778–782. doi: 10.1056/NEJM197010082831502. [DOI] [PubMed] [Google Scholar]
  6. Evensen S. A., Shepro D. DNA synthesis in rat aortic endothelium; effect of bacterial endotoxin and trauma. Microvasc Res. 1974 Jul;8(1):90–96. doi: 10.1016/0026-2862(74)90067-3. [DOI] [PubMed] [Google Scholar]
  7. Fearon D. T., Ruddy S., Schur P. H., McCabe W. R. Activation of the properdin pathway of complement in patients with gram-negative of bacteremia. N Engl J Med. 1975 May 1;292(18):937–940. doi: 10.1056/NEJM197505012921802. [DOI] [PubMed] [Google Scholar]
  8. From A. H., Gewurz H., Gruninger R. P., Pickering R. J., Spink W. W. Complement in endotoxin shock: effect of complement depletion on the early hypotensive phase. Infect Immun. 1970 Jul;2(1):38–41. doi: 10.1128/iai.2.1.38-41.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. GILBERT R. P. Mechanisms of the hemodynamic effects of endotoxin. Physiol Rev. 1960 Apr;40:245–279. doi: 10.1152/physrev.1960.40.2.245. [DOI] [PubMed] [Google Scholar]
  10. GILBERT V. E., BRAUDE A. I. Reduction of serum complement in rabbits after injection of endotoxin. J Exp Med. 1962 Oct 1;116:477–490. doi: 10.1084/jem.116.4.477. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Galanos C., Lüderitz O., Westphal O. A new method for the extraction of R lipopolysaccharides. Eur J Biochem. 1969 Jun;9(2):245–249. doi: 10.1111/j.1432-1033.1969.tb00601.x. [DOI] [PubMed] [Google Scholar]
  12. Garner R., Chater B. V., Brown D. L. The role of complement in endotoxin shock and disseminated intravascular coagulation: experimental observations in the dog. Br J Haematol. 1974 Nov;28(3):393–401. doi: 10.1111/j.1365-2141.1974.tb00820.x. [DOI] [PubMed] [Google Scholar]
  13. Gordon S., Unkeless J. C., Cohn Z. A. Induction of macrophage plasminogen activator by endotoxin stimulation and phagocytosis: evidence for a two-stage process. J Exp Med. 1974 Oct 1;140(4):995–1010. doi: 10.1084/jem.140.4.995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Guenter C. A., Fiorica V., Hinshaw L. B. Cardiorespiratory and metabolic responses to liver E. coli and endotoxin in the monkey. J Appl Physiol. 1969 Jun;26(6):780–786. doi: 10.1152/jappl.1969.26.6.780. [DOI] [PubMed] [Google Scholar]
  15. Henson P. M., Cochrane C. G. Immunological induction of increased vascular permeability. II. Two mechanisms of histamine release from rabbit platelets involving complement. J Exp Med. 1969 Jan 1;129(1):167–184. doi: 10.1084/jem.129.1.167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Henson P. M. Complement-dependent platelet and polymorphonuclear leukocyte reactions. Transplant Proc. 1974 Mar;6(1):27–31. [PubMed] [Google Scholar]
  17. Johnson K. J., Ward P. A. Protective function of C6 in rabbits treated with bacterial endotoxin. J Immunol. 1971 Apr;106(4):1125–1127. [PubMed] [Google Scholar]
  18. KNIKER W. T., COCHRANE C. G. PATHOGENIC FACTORS IN VASULAR LESIONS OF EXPERIMENTAL SERUM SICKNESS. J Exp Med. 1965 Jul 1;122:83–98. doi: 10.1084/jem.122.1.83. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kitzmiller J. L., Lucas W. E., Yelenosky P. F. The role of complement in feline endotoxin shock. Am J Obstet Gynecol. 1972 Feb 1;112(3):414–421. doi: 10.1016/0002-9378(72)90488-7. [DOI] [PubMed] [Google Scholar]
  20. Lachmann P. J., Thompson R. A. Reactive lysis: the complement-mediated lysis of unsensitized cells. II. The characterization of activated reactor as C56 and the participation of C8 and C9. J Exp Med. 1970 Apr 1;131(4):643–657. doi: 10.1084/jem.131.4.643. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Mancini G., Carbonara A. O., Heremans J. F. Immunochemical quantitation of antigens by single radial immunodiffusion. Immunochemistry. 1965 Sep;2(3):235–254. doi: 10.1016/0019-2791(65)90004-2. [DOI] [PubMed] [Google Scholar]
  22. McCabe W. R. Gram-negative bacteremia. Adv Intern Med. 1974;19:135–158. [PubMed] [Google Scholar]
  23. McCabe W. R. Serum complement levels in bacteremia due to gram-negative organisms. N Engl J Med. 1973 Jan 4;288(1):21–23. doi: 10.1056/NEJM197301042880105. [DOI] [PubMed] [Google Scholar]
  24. McCall C. E., De Chatelet L. R., Brown D., Lachmann P. New biological activity following intravascular activation of the complement cascade. Nature. 1974 Jun 28;249(460):841–843. doi: 10.1038/249841a0. [DOI] [PubMed] [Google Scholar]
  25. McGrath J. M., Stewart G. J. The effects of endotoxin on vascular endothelium. J Exp Med. 1969 May 1;129(5):833–848. doi: 10.1084/jem.129.5.833. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. McKay D. G. Vessel wall and thrombogenesis--endotoxin. Thromb Diath Haemorrh. 1973 Feb 28;29(1):11–26. [PubMed] [Google Scholar]
  27. Melmon K. L., Cline M. J. The interaction of leukocytes and the kinin system. Biochem Pharmacol. 1968 Mar;(Suppl):271–281. doi: 10.1016/0006-2952(68)90313-4. [DOI] [PubMed] [Google Scholar]
  28. Mergenhagen S. E., Snyderman R., Gewurz H., Shin H. S. Significance of complement to the mechanism of action of endotoxin. Curr Top Microbiol Immunol. 1969;50:37–77. doi: 10.1007/978-3-642-46169-9_2. [DOI] [PubMed] [Google Scholar]
  29. Morrison D. C., Cochrane C. G. Direct evidence for Hageman factor (factor XII) activation by bacterial lipopolysaccharides (endotoxins). J Exp Med. 1974 Sep 1;140(3):797–811. doi: 10.1084/jem.140.3.797. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Morrison D. C., Leive L. Fractions of lipopolysaccharide from Escherichia coli O111:B4 prepared by two extraction procedures. J Biol Chem. 1975 Apr 25;250(8):2911–2919. [PubMed] [Google Scholar]
  31. Müller-Berghaus G., Lohmann E. The role of complement in endotoxin-induced disseminated intravascular coagulation: studies in congenitally C6-deficient rabbits. Br J Haematol. 1974 Nov;28(3):403–418. doi: 10.1111/j.1365-2141.1974.tb00821.x. [DOI] [PubMed] [Google Scholar]
  32. Phillips J. K., Snyderman R., Mergenhagen S. E. Activation of complement by endotoxin: a role for 2 globulin, C1, C4 and C2 in the consumption of terminal complement components by endotoxin-coated erythrocytes. J Immunol. 1972 Aug;109(2):334–341. [PubMed] [Google Scholar]
  33. Rivers R. P., Hathaway W. E., Weston W. L. The endotoxin-induced coagulant activity of human monocytes. Br J Haematol. 1975 Jul;30(3):311–316. doi: 10.1111/j.1365-2141.1975.tb00547.x. [DOI] [PubMed] [Google Scholar]
  34. Snyderman R., Pike M. C. Interaction of complex polysaccharides with the complement system: effect of calcium depletion on terminal component consumption. Infect Immun. 1975 Feb;11(2):273–279. doi: 10.1128/iai.11.2.273-279.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Stewart G. J., Anderson M. J. An ultrastructural study of endotoxin induced damage in rabbit mesenteric arteries. Br J Exp Pathol. 1971 Feb;52(1):75–80. [PMC free article] [PubMed] [Google Scholar]
  36. Ward P. A., Hill J. H. C5 chemotactic fragments produced by an enzyme in lysosomal granules of neutrophils. J Immunol. 1970 Mar;104(3):535–543. [PubMed] [Google Scholar]
  37. Zimmerman T. S., Arroyove C. M., Müller-Eberhard H. J. A blood coagulation abnormality in rabbits deficient in the sixth component of complement (C6) and its correction by purified C6. J Exp Med. 1971 Dec 1;134(6):1591–1600. doi: 10.1084/jem.134.6.1591. [DOI] [PMC free article] [PubMed] [Google Scholar]

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