A Physiologic Regulator of Collagen-Induced Platelet Aggregation: Inhibition by Clq

Summary

Platelet aggregations were studied by a turbidimetric method in citrated human platelet-rich plasmas (PRP) in vitro. Human Clq inhibited the aggregations caused by collagens derived from different tissues and species. Clq was needed by weight in comparable quantities to collagen for neutralizing the aggregating effect. The dependence of the inhibitory reaction on the preincubation of platelets with Clq and the differences in the occurrence of aggregating substances in supernatants of PRP triggered with collagen in the presence or absence of Clq, confirmed that Clq exerts its effect by preventing fixation of collagen to platelets. In addition, the high specificity of the inhibitory action of Clq for collagen-induced platelet aggregation was demonstrated by results obtained for testing a variety of aggregating agents in combination with Clq and/or collagen.

Since normal concentrations of Clq in the blood are in the range of inhibitory doses of Clq for collagen-induced platelet aggregations in vitro and upon activation of complement Clq is known to dissociate from Cl, it is proposed that Clq may participate in a highly specific manner in regulating platelet reactivity to collagen in vivo.

Keywords

Platelets - Subcomponent Clq - Collagen

• References

• 1 Müller-Eberhard HJ. Complement. Annu Rev Biochem 1969; 38: 389-414
• 2 Yonemasu K, Stroud RM, Niedermeier W, Butler WT. Chemical studies on Clq: a modulator of immunoglobulin biology. Biochem Biophys Res Commun 1971; 43: 1388-1394
• 3 Calcott MA, Müller-Eberhard HJ. Clq protein of human complement. Biochemistry 1972; 11: 3443-3450
• 4 Reid KB M, Lowe DM, Porter RR. Isolation and characterization of Clq, a subcomponent of the first component of complement, from human and rabbit sera. Biochem J 1972; 130: 749-763
• 5 Knobel HR, Heusser C, Rodrick ML, Isliker H. Enzymatic digestion of the first component of human complement (Clq). J Immunol 1974; 112: 2094-2101
• 6 Knobel HR, Villiger W, Isliker R. Chemical analysis and electron microscopy studies of human Clq prepared by different methods. Eur J Immunol 1975; 5: 78-82
• 7 Brodsky-Doyle B, Leonard KR, Reid KBM. Circular-dichroism and electron-microscopy studies of human subcomponent Clq before and after limited proteolysis by pepsin. Biochem J 1976; 159: 279-286
• 8 Porter RR, Reid KB M. The biochemistry of complement. Nature 1978; 275: 699-704
• 9 Suba EA, Csákó G. Clq(Cl) receptor on human platelets: Inhibition of collagen-induced platelet aggregation by Clq(Cl) molecules. J Immunol 1976; 117: 304-309
• 10 Csákó G, Suba EA, Herp A. Similarities and dissimilarities between the binding ability of Clq and collagen. Clin Exp Immunol. 1981 in press.
• 11 Allan R, Rodrick M, Knobel HR, Isliker H. Inhibition of the interaction between the complement component Clq and immune complexes. Int Arch Allergy Appl Immunol 1979; 58: 140-148
• 12 Cazenave J-P, Assimeh SN, Painter RH, Packham MA, Mustard JF. Clq inhibition of the interaction of collagen with human platelets. J Immunol 1976; 116: 162-163
• 13 Wautier J-L, Souchon H, Reid KB M, Peltier AP, Caen JP. Studies on the mode of reaction of the first component of complement with platelets; Interaction between the collagen-like portion of Clq and platelets. Immunochemistry 1977; 14: 763-766
• 14 Agnello V, Winchester RJ, Kunkel HG. Precipitin reactions of the Clq component of complement with aggregated γ-globulin and immune complexes in gel diffusion. Immunology 1970; 19: 909-919
• 15 Rapp HJ, Borsos T. Molecular Basis of Complement Action. Appleton-Century-Crofts; New York: 1970
• 16 Gigli I, Porter RR, Sim RB. The unactivated form of the first component of human complement, C1. Biochem J 1976; 157: 541-548
• 17 Csákó G, Suba EA, Wistar Jr R. Activation of human platelets by antibodies to thymocytes and β₂-microglobulin. I. Qualitative and quantitative aspects of the platelet aggregation induced by HATG and SA;₂2mG. Clin Exp Immunol 1980; 39: 461-469
• 18 Shulman NR, Marder VJ, Hiller MC, Collier EM. Platelet and leukocyte isoantigens and their antibodies: Serologic, physiologic and clinical studies. Prog Hematol 1964; 4: 222-304
• 19 Lüscher EF, Davey MG. The initiation of viscous metamorphosis of the blood platelets. In: Johnson SA, Seegers WH. (eds.), Physiology of Hemostasis and Thrombosis. C. V. Thomas Publisher; Springfield, Illinois: 1967. pp. 09-21
• 20 Scheidegger JJ. Une microméthode de l’immunoelectrophorese. Int Arch Allergy Appl Immunol 1955; 7: 103-110
• 21 Traub W, Piez KA. The chemistry and structure of collagen. Adv Protein Chem 1971; 25: 243-352
• 22 Muggli R, Baumgartner HR. Collagen induced platelet aggregation: requirement for tropocollagen multimers. Thromb Res 1973; 3: 715-728
• 23 Ziccardi RJ, Cooper NR. Demonstration and quantitation of activation of the first component of complement in human sera. J Exp Med 1978; 147: 385-395
• 24 Laurell AB, Johnson U, Mårtenson U, Sjüholm AG. Formation of Complexes composed of CĪr, CĪs, and Cl inactivator in human serum on activation of Cl. Acta Pathol Microbiol Scand [C] 1978; 86: 299-306
• 25 Ziccardi RJ, Cooper NR. Modulation of the antigenicity of Clr and CĪs by CĪ inactivator. J Immunol 1978; 121: 2148-2152
• 26 Pickering RJ, Naff GB, Stroud RM, Good RA, Gewurz H. Deficiency of Clr in human serum. Effects on the structure and function of macromolecular Cl. J Exp Med 1970; 131: 803-815
• 27 Nakanishi M, Imamura H, Goto K. Potentiation of the ADP-induced platelet aggregation by collagen and its inhibition by a tetrahydrothienopyridine derivative (Y-3642). Biochem Pharmacol 1971; 20: 2116-2118
• 28 Packham MA, Guccione MA, Chang P-L, Mustard JF. Platelet aggregation and release: effects of low concentrations of thrombin or collagen. Am J Physiol 1973; 225: 38-47
• 29 Bjornson HS, Hill EO. Bacteroidacaea in thromboembolic disease: effects of cell wall components on blood coagulation in vivo and in vitro. Infect Immun 1973; 8: 911-918
• 30 Salzman EW. Studies on the mechanism of platelet aggregation by adenosine diphosphate. In: Johnson SA, Seegers WH. (eds.), Physiology of Hemostasis and Thrombosis, C. C. Thomas Publisher; Springfield, Illinois: 1967. pp. 140-153
• 31 Semeraro N, Fumarola D, Mertens F, Vermylen J. Evidence that endotoxins enhance the Factor X activator activity of washed human platelets. Br J Haematol 1978; 38: 243-249