Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1986 Nov;78(5):1136–1141. doi: 10.1172/JCI112693

Human platelet aggregation is initiated by peripheral blood mononuclear cells exposed to bacterial lipopolysaccharide in vitro.

B S Schwartz, M C Monroe
PMCID: PMC423795  PMID: 3533997

Abstract

Platelet consumption is a prominent feature of disseminated intravascular coagulation. We investigated whether monocyte procoagulant activity (PCA) might play a role in platelet consumption associated with gram-negative septicemia. Human mononuclear cells exposed in vitro to lipopolysaccharide demonstrated parallel dose-dependent increases in PCA and ability to induce platelet aggregation. Induction of platelet aggregation required the generation of thrombin dependent on coagulation Factors VII, X, and II, and calcium. This is consistent with monocyte tissue factor initiating thrombin generation. A specific monoclonal antimonocyte antibody was used to identify monocytes via indirect immunofluorescence, and demonstrated that all monocytes were included in platelet aggregates. Mononuclear cells that did not express PCA did not induce platelet aggregation and monocytes were not surrounded by platelet clumps. These data suggest that monocytes induced to express tissue factor on their surface may be important mediators of endotoxin-induced platelet, as well as fibrinogen, consumption.

Full text

PDF
1136

Images in this article

1139Image
on p.1139
1140Image
on p.1140

Selected References

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

  1. Ausprunk D. H., Das J. Endotoxin-induced changes in human platelet membranes: morphologic evidence. Blood. 1978 Mar;51(3):487–495. [PubMed] [Google Scholar]
  2. Bar-Shavit R., Kahn A., Wilner G. D., Fenton J. W., 2nd Monocyte chemotaxis: stimulation by specific exosite region in thrombin. Science. 1983 May 13;220(4598):728–731. doi: 10.1126/science.6836310. [DOI] [PubMed] [Google Scholar]
  3. Beller F. K. The role of endotoxin in disseminated intravascular coagulation. Thromb Diath Haemorrh Suppl. 1969;36:125–149. [PubMed] [Google Scholar]
  4. Corrigan J. J., Jr, Ray W. L., May N. Changes in the blood coagulation system associated with septicemia. N Engl J Med. 1968 Oct 17;279(16):851–856. doi: 10.1056/NEJM196810172791603. [DOI] [PubMed] [Google Scholar]
  5. Dimitriu-Bona A., Burmester G. R., Waters S. J., Winchester R. J. Human mononuclear phagocyte differentiation antigens. I. Patterns of antigenic expression on the surface of human monocytes and macrophages defined by monoclonal antibodies. J Immunol. 1983 Jan;130(1):145–152. [PubMed] [Google Scholar]
  6. Edwards R. L., Rickles F. R., Bobrove A. M. Mononuclear cell tissue factor: cell of origin and requirements for activation. Blood. 1979 Aug;54(2):359–370. [PubMed] [Google Scholar]
  7. Edwards R. L., Rickles F. R. Macrophage procoagulants. Prog Hemost Thromb. 1984;7:183–209. [PubMed] [Google Scholar]
  8. Ginsberg M. H., Henson P. M. Enhancement of platelet response to immune complexes and IgG aggregates by lipid A-rich bacterial lipopolysaccharides. J Exp Med. 1978 Jan 1;147(1):207–217. doi: 10.1084/jem.147.1.207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Goodnough L. T., Saito H. Specific binding of thrombin by human peripheral blood monocytes: possible role in the clearance of activated clotting factors from the circulation. J Lab Clin Med. 1982 Jun;99(6):873–884. [PubMed] [Google Scholar]
  10. Han P., Turpie A. G., Genton E. Plasma beta-thromboglobulin: differentiation between intravascular and extravascular platelet destruction. Blood. 1979 Nov;54(5):1192–1196. [PubMed] [Google Scholar]
  11. Horn R. G., Collins R. D. Studies on the pathogenesis of the generalized Schwartzman reaction. The role of granulocytes. Lab Invest. 1968 Feb;18(2):101–107. [PubMed] [Google Scholar]
  12. Jungi T. W., Spycher M. O., Nydegger U. E., Barandun S. Platelet-leukocyte interaction: selective binding of thrombin-stimulated platelets to human monocytes, polymorphonuclear leukocytes, and related cell lines. Blood. 1986 Mar;67(3):629–636. [PubMed] [Google Scholar]
  13. Kaplan K. L., Owen J. Plasma levels of beta-thromboglobulin and platelet factor 4 as indices of platelet activation in vivo. Blood. 1981 Feb;57(2):199–202. [PubMed] [Google Scholar]
  14. Kociba G. J., Griesemer R. A. Disseminated intravascular coagulation induced with leukocyte procoagulant. Am J Pathol. 1972 Dec;69(3):407–420. [PMC free article] [PubMed] [Google Scholar]
  15. Kornecki E., Tuszynski G. P., Niewiarowski S. Inhibition of fibrinogen receptor-mediated platelet aggregation by heterologous anti-human platelet membrane antibody. Significance of an Mr = 66,000 protein derived from glycoprotein IIIa. J Biol Chem. 1983 Aug 10;258(15):9349–9356. [PubMed] [Google Scholar]
  16. LEVIN J., CLUFF L. E. PLATELETS AND THE SHWARTZMAN PHENOMENON. J Exp Med. 1965 Feb 1;121:235–246. doi: 10.1084/jem.121.2.235. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Laudano A. P., Doolittle R. F. Synthetic peptide derivatives that bind to fibrinogen and prevent the polymerization of fibrin monomers. Proc Natl Acad Sci U S A. 1978 Jul;75(7):3085–3089. doi: 10.1073/pnas.75.7.3085. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. 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]
  19. 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]
  20. Mosher D. F., Doyle M. J., Jaffe E. A. Synthesis and secretion of thrombospondin by cultured human endothelial cells. J Cell Biol. 1982 May;93(2):343–348. doi: 10.1083/jcb.93.2.343. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Nossel H. L., Wasser J., Kaplan K. L., LaGamma K. S., Yudelman I., Canfield R. E. Sequence of fibrinogen proteolysis and platelet release after intrauterine infusion of hypertonic saline. J Clin Invest. 1979 Nov;64(5):1371–1378. doi: 10.1172/JCI109594. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Patscheke H. Shape and functional properties of human platelets washed with acid citrate. Haemostasis. 1981;10(1):14–27. doi: 10.1159/000214383. [DOI] [PubMed] [Google Scholar]
  23. Ross R. The pathogenesis of atherosclerosis--an update. N Engl J Med. 1986 Feb 20;314(8):488–500. doi: 10.1056/NEJM198602203140806. [DOI] [PubMed] [Google Scholar]
  24. Siegal T., Seligsohn U., Aghai E., Modan M. Clinical and laboratory aspects of disseminated intravascular coagulation (DIC): a study of 118 cases. Thromb Haemost. 1978 Feb 28;39(1):122–134. [PubMed] [Google Scholar]
  25. THOMAS L., GOOD R. A. Studies on the generalized Shwartzman reaction: I. General observations concerning the phenomenon. J Exp Med. 1952 Dec;96(6):605–624. doi: 10.1084/jem.96.6.605. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Tsao B. P., Fair D. S., Curtiss L. K., Edgington T. S. Monocytes can be induced by lipopolysaccharide-triggered T lymphocytes to express functional factor VII/VIIa protease activity. J Exp Med. 1984 Apr 1;159(4):1042–1057. doi: 10.1084/jem.159.4.1042. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Yoshikawa T., Tanaka K. R., Guze L. B. Infection and disseminated intravascular coagulation. Medicine (Baltimore) 1971 Jul;50(4):237–258. doi: 10.1097/00005792-197107000-00001. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES