Macrophage Inhibition of Collagen-Induced Platelet Aggregation

Summary

Collagen was incubated with cells or media fractions of mouse peritoneal macrophage cultures, and its aggregating effect on human platelets was tested. Incubation with lysates of cultured cells completely abolished the normal collagen-induced platelet aggregation, while incubation with media fractions only caused partial inhibition. The latter inhibition was more pronounced after macrophage phagocytosis of latex particles, while endocytosis of endotoxin had no effect.

Corresponding macrophage cultures were also tested for specific collagenase activity, using ¹⁴C-glycine labelled collagen as substrate. Collagenase activity was found in the culture media fractions only, and the enzyme activity could be enhanced by endocytosis of latex as well as endotoxin.

It appears that the effect of macrophage lysates and media on collagen-platelet interaction cannot be ascribed only to secretion of collagenase from macrophages.

• References

• 1 Born GV R. 1962; Aggregation of blood platelets by adenosine diphosphate and its reversal. Nature 194: 927
• 2 Brass LF, Bensusan HB. 1974; The role of collagen quaternary structure in the platelet: collagen interaction. The Journal of Clinical Investigation 54: 1480
• 3 Caen JP, Legrand Y. 1968; L’analyse des functions plaquettaires. Adhesion et agrégation des plaquettes au collagène purifié Revue française d’études cliniques et biologiques 13: 1028
• 4 Chesney CMc I, Harper E, Colman RW. 1972; Critical role of the carbohydrate side chains of collagen in platelet aggregation. The Journal of Clinical Investigation 51: 2693
• 5 Cohn ZA, Benson B. 1965; The differentiation of mononuclear phagocytes. Morphology, cytochemistry, and biochemistry The Journal of Experimental Medicine 121: 153
• 6 Dannenberg jr AM. 1975; Macrophages in inflammation and infection. The New England Journal of Medicine Sept. 4: 489
• 7 Gaarder A, Jonsen J, Laland S, Hellem A, Owren PA. 1961; Adenosine diphosphate in red cells as a factor in the adhesiveness of human blood platelets. Nature 192: 531
• 8 Harris ED, Krane SM. 1974; Collagénases. The New England Journal of Medicine 291, 557 605: 625
• 9 Hovig T. 1963; Aggregation of rabbit blood platelets produced in vitro by saline “extracts” of tendons. Thrombosis et Diathesis haemorrhagica 9: 248
• 10 Houck J, Chang C. 1971; Platelet aggregation produced by collagenolysis product peptides. Proceedings of the Society for Experimental Biology and Medicine 138: 342
• 11 Humes JL, Bonney RJ, Relus L, Dahlgren ME, Sadowski SJ, Kuehl jr FA, Davies P. 1977; Macrophages synthesize and release prostaglandins in response to inflammatory stimuli. Nature 269: 149
• 12 Jaffe RM. 1976. Interaction of platelets with connective tissue. In GORDON JL. (ed.) Platelets in Biology and Pathology. Elsevier, North-Holland, Biomedical Press; p 261
• 13 Jaffe R, Deykin D. 1974; Evidence for a structural requirement for the aggregation of platelets by collagen. The Journal of Clinical Investigation 53: 875
• 14 Kang AH, Nagai Y, Piez KA, Gross J. 1966; Studies on the structure of collagen utilizing a collagenolytic enzyme from tadpole. Biochemistry 5: 509
• 15 Katzman RL, Kang AH, Beachey EH. 1973; Collagen-induced platelet aggregation: Involvement of an active glycopeptide fragment (α_l-CB5). Science 181: 670
• 16 Mørland B, Kaplan G. 1977; Macrophage activation in vivo and in vitro. Experimental Cell Research 108: 279
• 17 Mørland B, Mørland J. 1978; Selective induction of lysosomal enzyme activities in mouse peritoneal macrophages. Journal of the Reticuloendothelial Society 23: 469
• 18 Muggli R, Baumgartner HR. 1973; Collagen induced platelet aggregation: Requirement for tropo collagen multimers. Thrombosis Research 3: 715
• 19 Page RC, Davies P, Allison AC. 1974; Participation of mononuclear phagocytes in chronic inflammatory diseases. Journal of reticuloendothelial Society 15: 413
• 20 Prydz H, Allison AC. 1978; Tissue thromboplastin activity of isolated human monocytes. Thrombosis Haemostasis 39: 582
• 21 Santoro SA, Cunningham LW. 1977; Collagen mediated platelet aggregation. Evidence for multivalent interactions of intermediate specificity between collagen and platelets The Journal of Clinical Investigation 60: 1054
• 22 Seifter S, Harper E. 1970. Collagenases. In Colowick SP, Kaplan ND. (eds.) Methods in enzymology. Vol. XIX Academic Press; p 613
• 23 Unanue ER. 1976; Secretory function of mononuclear phagocytes. A Review. American Journal of Pathology 83: 396
• 24 Wahl LM, Wahl SM, Mergenhagen SE, Martin GR. 1974; Collagenase production by endotoxin-activated macrophages. National Academy of Sciences. Proceedings 71: 3598
• 25 Werb Z, Gordon S. 1975; Secretion of a specific collagenase by stimulated macrophages. The Journal of Experimental Medicine 142: 346
• 26 Wilner GD, Nossel HL, Leroy EC. 1968; Aggregation of platelets by collagen. The Journal of Clinical Investigation 47: 2616
• 27 Woessner jr JF. 1968. Biological mechanisms of collagen resorption. In Gould BS. (ed.) Treatise on collagen, vol. 2B. Academic Press; New York: p 253
• 28 Zucker MB, Borrelli J. 1962; Platelet clumping produced by connective tissue suspensions and by collagen. Society for Experimental Biology and Medicine Proceedings 109: 119