Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1974 Dec;54(6):1437–1443. doi: 10.1172/JCI107891

The Stimulatory Effect of Platelets and Platelet Membranes on the Procoagulant Activity of Leukocytes

Julian Niemetz 1,2,3,4, Aaron J Marcus 1,2,3,4
PMCID: PMC301699  PMID: 4612059

Abstract

Leukocytes can generate procoagulant (tissue factor) activity when incubated with endotoxin. These studies were undertaken to determine whether platelets could influence the procoagulant activity generated by leukocytes. Intact or disrupted platelets (rabbit or human) enhanced the clot-promoting properties of rabbit leukocytes.

The enhancing effect of human platelets on human leukocytes required the presence of human serum (devoid of factor VII and X activities). When platelets were incubated with endotoxin in the absence of leukocytes, no increase in their clot-promoting properties was discernible. However, a mixture of platelets, leukocytes, and endotoxin generated procoagulant activity which appeared rapidly and was fivefold greater than that produced by leukocytes incubated with endotoxin alone. The enhancement produced by platelets was even more pronounced if homogenates were used. The platelet effect was examined in more detail by the substitution of membranes, granules, and the “soluble” fraction for whole platelets in the test system. The stimulating activity was localized to the particulate fractions, i.e., membranes and granules. Prior treatment of platelet membranes with phospholipase C or gangliosides or by extraction of lipid resulted in loss of enhancing activity, whereas no inhibition was observed after exposure to neuraminidase or trypsin. It is proposed that platelets contribute a membrane lipoprotein surface which enhances the procoagulant activity generated by leukocytes in the presence of endotoxin. This mechanism may be involved in some of the clinical and pathologic manifestations of gram-negative sepsis with disseminated intravascular coagulation.

Full text

PDF
1437

Selected References

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

  1. Ardlie N. G., Packham M. A., Mustard J. F. Adenosine diphosphate-induced platelet aggregation in suspensions of washed rabbit platelets. Br J Haematol. 1970 Jul;19(1):7–17. doi: 10.1111/j.1365-2141.1970.tb01596.x. [DOI] [PubMed] [Google Scholar]
  2. Ardlie N. G., Perry D. W., Packham M. A., Mustard J. F. Influence of apyrase on stability of suspensions of washed rabbit platelets. Proc Soc Exp Biol Med. 1971 Apr;136(4):1021–1023. doi: 10.3181/00379727-136-35419. [DOI] [PubMed] [Google Scholar]
  3. Biggs R., Denson K. W., Riesenberg D., McIntyre C. The coagulant activity of platelets. Br J Haematol. 1968 Sep;15(3):283–296. doi: 10.1111/j.1365-2141.1968.tb01539.x. [DOI] [PubMed] [Google Scholar]
  4. Cuatrecasas P. Gangliosides and membrane receptors for cholera toxin. Biochemistry. 1973 Aug 28;12(18):3558–3566. doi: 10.1021/bi00742a032. [DOI] [PubMed] [Google Scholar]
  5. EISEMAN G., STEFANINI M. Thromboplastic activity of leukemic white cells. Proc Soc Exp Biol Med. 1954 Aug-Sep;86(4):763–765. doi: 10.3181/00379727-86-21226. [DOI] [PubMed] [Google Scholar]
  6. GLYNN M. F., MOVAT H. Z., MURPHY E. A., MUSTARD J. F. STUDY OF PLATELET ADHESIVENESS AND AGGREGATION, WITH LATEX PARTICLES. J Lab Clin Med. 1965 Feb;65:179–201. [PubMed] [Google Scholar]
  7. Garg S. K., Niemetz J. Tissue factor activity of normal and leukemic cells. Blood. 1973 Nov;42(5):729–735. [PubMed] [Google Scholar]
  8. Graeff H., Beller F. K. Hematological studies during endotoxin infusion in rabbits. Thromb Diath Haemorrh. 1968 Dec 31;20(3):420–429. [PubMed] [Google Scholar]
  9. Gralnick H. R., Abrell E. Studies of the procoagulant and fibrinolytic activity of promyelocytes in acute promyelocytic leukaemia. Br J Haematol. 1973 Jan;24(1):89–99. doi: 10.1111/j.1365-2141.1973.tb05730.x. [DOI] [PubMed] [Google Scholar]
  10. Kociba G. J., Loeb W. F., Wall R. L. Development of procoagulant (tissue thromboplastin) activity in cultured leukocytes. J Lab Clin Med. 1972 May;79(5):778–787. [PubMed] [Google Scholar]
  11. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  12. 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]
  13. MARTIN H., ROKA L. Beeinflussung der Blutgerinnung durch Leukocyten. Klin Wochenschr. 1951 Aug 1;29(29-30):510–512. doi: 10.1007/BF01483627. [DOI] [PubMed] [Google Scholar]
  14. Marcus A. J., Ullman H. L., Safier L. B. Studies on human platelet gangliosides. J Clin Invest. 1972 Oct;51(10):2602–2612. doi: 10.1172/JCI107078. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Marcus A. J., Zucker-Franklin D., Safier L. B., Ullman H. L. Studies on human platelet granules and membranes. J Clin Invest. 1966 Jan;45(1):14–28. doi: 10.1172/JCI105318. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. McKAY D. G., SHAPIRO S. S. Alterations in the blood coagulation system induced by bacterial endotoxin. I. In vivo (generalized Shwartzman reaction). J Exp Med. 1958 Mar 1;107(3):353–367. doi: 10.1084/jem.107.3.353. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Nemerson Y. The reaction between bovine brain tissue factor and factors VII and X. Biochemistry. 1966 Feb;5(2):601–608. doi: 10.1021/bi00866a029. [DOI] [PubMed] [Google Scholar]
  18. Niemetz J. Coagulant activity of leukocytes. Tissue factor activity. J Clin Invest. 1972 Feb;51(2):307–313. doi: 10.1172/JCI106815. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Niemetz J., Fani K. Thrombogenic activity of leukocytes. Blood. 1973 Jul;42(1):47–59. [PubMed] [Google Scholar]
  20. Niemetz J., Herbert V. The role of protein synthesis on the generation of tissue factor activity by leukocytes. Proc Soc Exp Biol Med. 1972 Apr;139(4):1276–1279. doi: 10.3181/00379727-139-36346. [DOI] [PubMed] [Google Scholar]
  21. Rapaport S. I., Hjort P. F. The blood clotting properties of rabbit peritoneal leukocytes in vitro. Thromb Diath Haemorrh. 1967 Feb 28;17(1-2):222–236. [PubMed] [Google Scholar]
  22. Rickles F. R., Hardin J. A., Pitlick F. A., Hoyer L. W., Conrad M. E. Tissue factor activity in lymphocyte cultures from normal individuals and patients with hemophilia A. J Clin Invest. 1973 Jun;52(6):1427–1434. doi: 10.1172/JCI107316. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Saba H. I., Herion J. C., Walker R. I., Roberts H. R. The procoagulant activity of granulocytes. Proc Soc Exp Biol Med. 1973 Feb;142(2):614–620. doi: 10.3181/00379727-142-37078. [DOI] [PubMed] [Google Scholar]
  24. Tóth S., Szilágyi T., Went M., Lévai G. Preparation of local Shwartzman reaction by means of platelet rich plasma. Acta Physiol Acad Sci Hung. 1972;42(2):163–168. [PubMed] [Google Scholar]

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

RESOURCES