Skip to main content
NCBI home page
Infection and Immunity logoLink to Infection and Immunity
. 1990 Jun;58(6):1821–1827. doi: 10.1128/iai.58.6.1821-1827.1990

Disparate mechanisms of induction of procoagulant activity by live and inactivated bacteria and viruses.

S B Sinclair 1, O D Rotstein 1, G A Levy 1
PMCID: PMC258730  PMID: 2160434

Abstract

This study describes the dose response, time course, and lymphocyte requirements of procoagulant activity (PCA) induction following stimulation of thioglycolate-elicited BALB/c peritoneal macrophages with live and inactivated bacteria (Bacteroides fragilis, Escherichia coli, and Staphylococcus aureus) and murine hepatitis virus type 3 (MHV-3). Induction of PCA by MHV-3 was significantly more rapid and the maximal PCA achieved was significantly greater than by the three bacterial species studied. In relation to induction of PCA by bacteria, the PCA response was more rapid and of greater magnitude with S. aureus and E. coli than with B. fragilis. MHV-3 induced an augmented PCA response at all concentrations of virus studied in a dose-dependent fashion, whereas higher titers of live bacteria (greater than 10(7) CFU/ml) inhibited PCA, suggesting the production of an inhibitory factor. Significant PCA induction was observed when macrophages were incubated with bacteria or virus in the absence of lymphocytes. At low titers of B. fragilis (10(3) CFU/ml), addition of lymphocytes greatly augmented PCA production, whereas at higher titers (10(7) CFU/ml), the addition of lymphocytes only slightly augmented the PCA response. In contrast, MHV-3 induction of PCA was enhanced by the addition of lymphocytes at all concentrations of virus studied, suggesting a lymphocyte-dependent process. Heat-inactivated bacteria were as effective as live bacteria in inducing PCA, suggesting that induction of PCA by bacteria requires only a bacterial surface component. In contrast, UV-inactivated MHV-3 did not induce PCA, suggesting that viral replication is a necessary step in PCA induction. These results suggest that the cellular and metabolic requirements for induction of PCA differ among viral and bacterial pathogens and may partly explain their differences in pathogenicity.

Full text

PDF
1821

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ahrenholz D. H., Simmons R. L. Fibrin in peritonitis. I. Beneficial and adverse effects of fibrin in experimental E. coli peritonitis. Surgery. 1980 Jul;88(1):41–47. [PubMed] [Google Scholar]
  2. Almdahl S. M., Brox J. H., Osterud B. Mononuclear phagocyte thromboplastin and endotoxin in patients with secondary bacterial peritonitis. Scand J Gastroenterol. 1987 Oct;22(8):914–918. doi: 10.3109/00365528708991935. [DOI] [PubMed] [Google Scholar]
  3. Almdahl S. M., Osterud B. Experimental gram-negative peritonitis: decreased thromboplastin activity in organs with a simultaneous rise of thromboplastin in blood monocytes and peritoneal macrophages. Res Exp Med (Berl) 1986;186(5):317–324. doi: 10.1007/BF01852097. [DOI] [PubMed] [Google Scholar]
  4. Boyum A. Separation of blood leucocytes, granulocytes and lymphocytes. Tissue Antigens. 1974;4(4):269–274. [PubMed] [Google Scholar]
  5. Chalkiadakis G., Kostakis A., Karayannacos P. E., Giamarellou H., Dontas I., Sakellariou I., Skalkeas G. D. The effect of heparin upon fibrinopurulent peritonitis in rats. Surg Gynecol Obstet. 1983 Sep;157(3):257–260. [PubMed] [Google Scholar]
  6. Ciano P. S., Colvin R. B., Dvorak A. M., McDonagh J., Dvorak H. F. Macrophage migration in fibrin gel matrices. Lab Invest. 1986 Jan;54(1):62–70. [PubMed] [Google Scholar]
  7. Colvin R. B., Johnson R. A., Mihm M. C., Jr, Dvorak H. F. Role of the clotting system in cell-mediated hypersensitivity. I. Fibrin deposition in delayed skin reactions in man. J Exp Med. 1973 Sep 1;138(3):686–698. doi: 10.1084/jem.138.3.686. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dindzans V. J., MacPhee P. J., Fung L. S., Leibowitz J. L., Levy G. A. The immune response to mouse hepatitis virus: expression of monocyte procoagulant activity and plasminogen activator during infection in vivo. J Immunol. 1985 Dec;135(6):4189–4197. [PubMed] [Google Scholar]
  9. Edwards R. L., Rickles F. R. The role of human T cells (and T cell products) for monocyte tissue factor generation. J Immunol. 1980 Aug;125(2):606–609. [PubMed] [Google Scholar]
  10. Geczy C. L., Roberts I. M., Meyer P., Bernard C. C. Susceptibility and resistance to experimental autoimmune encephalomyelitis and neuritis in the guinea pig correlate with the induction of procoagulant and anticoagulant activities. J Immunol. 1984 Dec;133(6):3026–3036. [PubMed] [Google Scholar]
  11. Hau T., Simmons R. L. Heparin in the treatment of experimental peritonitis. Ann Surg. 1978 Mar;187(3):294–298. doi: 10.1097/00000658-197803000-00014. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Holdsworth S. R., Tipping P. G. Macrophage-induced glomerular fibrin deposition in experimental glomerulonephritis in the rabbit. J Clin Invest. 1985 Oct;76(4):1367–1374. doi: 10.1172/JCI112112. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hopper K. E., Geczy C. L., Davies W. A. A mechanism of migration inhibition in delayed-type hypersensitivity reactions. I. Fibrin deposition on the surface of elicited peritoneal macrophages on vivo. J Immunol. 1981 Mar;126(3):1052–1058. [PubMed] [Google Scholar]
  14. Lando P. A., Edgington T. S. Lymphoid procoagulant response to bacterial endotoxin in the rat. Infect Immun. 1985 Dec;50(3):660–666. doi: 10.1128/iai.50.3.660-666.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Leibowitz J. L., Fung L. S., Levy G. A. A sensitive radioimmunoassay for the determination of antibodies to mouse hepatitis virus. J Virol Methods. 1983 May;6(5):255–265. doi: 10.1016/0166-0934(83)90040-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lerner R. G., Goldstein R., Cummings G., Lange K. Stimulation of human leukocyte thromboplastic activity by endotoxin. Proc Soc Exp Biol Med. 1971 Oct;138(1):145–148. doi: 10.3181/00379727-138-35848. [DOI] [PubMed] [Google Scholar]
  17. Levy G. A., Edgington T. S. Lymphocyte cooperation is required for amplification of macrophage procoagulant activity. J Exp Med. 1980 May 1;151(5):1232–1244. doi: 10.1084/jem.151.5.1232. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Levy G. A., Helin H., Edgington T. S. The pathobiology of viral hepatitis and immunologic activation of the coagulation protease network. Semin Liver Dis. 1984 Feb;4(1):59–68. doi: 10.1055/s-2008-1040646. [DOI] [PubMed] [Google Scholar]
  19. Levy G. A., Leibowitz J. L., Edgington T. S. Induction of monocyte procoagulant activity by murine hepatitis virus type 3 parallels disease susceptibility in mice. J Exp Med. 1981 Oct 1;154(4):1150–1163. doi: 10.1084/jem.154.4.1150. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Levy G. A., Schwartz B. S., Edgington T. S. The kinetics and metabolic requirements for direct lymphocyte induction of human procoagulant monokines by bacterial lipopolysaccharide. J Immunol. 1981 Jul;127(1):357–363. [PubMed] [Google Scholar]
  21. Levy G., Abecassis M. Activation of the immune coagulation system by murine hepatitis virus strain 3. Rev Infect Dis. 1989 May-Jun;11 (Suppl 4):S712–S721. doi: 10.1093/clinids/11.Supplement_4.S712. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lyberg T., Closs O., Prydz H. Effect of purified protein derivative and sonicates of Mycobacterium leprae and Mycobacterium bovis BCG on thromboplastin response in human monocytes in vitro. Infect Immun. 1982 Dec;38(3):855–859. doi: 10.1128/iai.38.3.855-859.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lyberg T., Nilsson K., Prydz H. Synthesis of thromboplastin by U-937 cells. Br J Haematol. 1982 Aug;51(4):631–641. doi: 10.1111/j.1365-2141.1982.tb02827.x. [DOI] [PubMed] [Google Scholar]
  24. Lyberg T., Prydz H. Is lymphocyte co-operation necessary for thromboplastin synthesis by human monocytes? Clin Exp Immunol. 1983 Sep;53(3):731–738. [PMC free article] [PubMed] [Google Scholar]
  25. Morrissey J. H., Fair D. S., Edgington T. S. Monoclonal antibody analysis of purified and cell-associated tissue factor. Thromb Res. 1988 Nov 1;52(3):247–261. doi: 10.1016/0049-3848(88)90084-9. [DOI] [PubMed] [Google Scholar]
  26. Osterud B., Flaegstad T. Increased tissue thromboplastin activity in monocytes of patients with meningococcal infection: related to an unfavourable prognosis. Thromb Haemost. 1983 Feb 28;49(1):5–7. [PubMed] [Google Scholar]
  27. Prydz H., Allison A. C. Tissue thromboplastin activity of isolated human monocytes. Thromb Haemost. 1978 Jun 30;39(3):582–591. [PubMed] [Google Scholar]
  28. Rosenthal G. A., Levy G., Rotstein O. D. Induction of macrophage procoagulant activity by Bacteroides fragilis. Infect Immun. 1989 Feb;57(2):338–343. doi: 10.1128/iai.57.2.338-343.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Rothberger H., Dove F. B., Lee T. K., McGee M. P., Kardon B. Procoagulant activity of lymphocyte-macrophage populations in rabbits: selective increases in marrow, blood, and spleen cells during Shwartzman reactions. Blood. 1983 Apr;61(4):712–717. [PubMed] [Google Scholar]
  30. Rotstein O. D., Kao J. Prevention of intra-abdominal abscesses by fibrinolysis using recombinant tissue plasminogen activator. J Infect Dis. 1988 Oct;158(4):766–772. doi: 10.1093/infdis/158.4.766. [DOI] [PubMed] [Google Scholar]
  31. Rotstein O. D., Pruett T. L., Simmons R. L. Fibrin in peritonitis. V. Fibrin inhibits phagocytic killing of Escherichia coli by human polymorphonuclear leukocytes. Ann Surg. 1986 Apr;203(4):413–419. doi: 10.1097/00000658-198604000-00013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Schiltknecht E., Ada G. L., Braciale T. J. Macrophage procoagulant-inducing activity of influenza-specific effector T cells. Cell Immunol. 1984 Dec;89(2):342–354. doi: 10.1016/0008-8749(84)90336-8. [DOI] [PubMed] [Google Scholar]
  33. Schwartz B. S., Edgington T. S. Lymphocyte collaboration is required for induction of murine monocyte procoagulant activity by immune complexes. J Immunol. 1981 Aug;127(2):438–443. [PubMed] [Google Scholar]
  34. Shands J. W., Jr Lymphocyte collaboration is not required for the induction of murine macrophage procoagulant by endotoxin. Thromb Res. 1987 Apr 15;46(2):271–279. doi: 10.1016/0049-3848(87)90289-1. [DOI] [PubMed] [Google Scholar]
  35. Sturman L. S., Ricard C. S., Holmes K. V. Proteolytic cleavage of the E2 glycoprotein of murine coronavirus: activation of cell-fusing activity of virions by trypsin and separation of two different 90K cleavage fragments. J Virol. 1985 Dec;56(3):904–911. doi: 10.1128/jvi.56.3.904-911.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. ZINSSER H. H., PRYDE A. W. Experimental study of physical factors, including fibrin formation, influencing the spread of fluids and small particles within and from the peritoneal cavity of the dog. Ann Surg. 1952 Nov;136(5):818–827. doi: 10.1097/00000658-195211000-00006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. van Ginkel C. J., Thörig L., Thompson J., Oh J. I., van Aken W. G. Enhancement of generation of monocyte tissue thromboplastin by bacterial phagocytosis: possible pathway for fibrin formation on infected vegetations in bacterial endocarditis. Infect Immun. 1979 Jul;25(1):388–395. doi: 10.1128/iai.25.1.388-395.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES