Studies on the Binding of Proteins to the Human Platelet Surface: Relation to Platelet Activation

Several antibody fractions and sera from patients with rheumatoid arthritis, systemic lupus erythematosus and chronic idiopathic thrombocytopenic purpura were examined for their ability to bind to normal platelets using immunofluorescent staining techniques. Platelet aggregometry was used to study the activating capacity of the samples.

Both C1q, C1s, C1 inactivator, fibrinogen, factor VIII-related antigen, alpha₁-acid glycoprotein, alpha₁-antitrypsin, beta₂-micro- globulin and isoantigens A and B, as well as fibronectin and plasminogen were found on the platelet surface. Only antibodies to C1q, C1s and beta₂-microglobulin were able to induce platelet aggregation. Sera containing immune complexes or platelet autoantibodies revealed positive surface staining for IgG, or for IgG and IgM. These sera also induced aggregation of platelets. Sera not containing immune complexes or autoantibodies gave negative staining and aggregation results. Thus, only some of the ligand receptor interactions were able to induce platelet aggregation.

Keywords

Human platelets - Protein binding - Immune complexes - Platelet autoantibodies - Aggregation - Immunofluorescence - Autoimmune diseases

PDF (646 kb)

Referenzen

References
1 Follea G, Mandrand B, Dechavanne M. Simultaneous enzymo- immunologic assays of platelet associated IgG, IgM and C₃ . A useful tool in assessment of immune thrombocytopenias Thromb Res 1982; 26: 249-258
2 Kayser W, Mueller-Eckhardt C, Bhakdi S, Ebert K. Platelet-associated complement C3 in thrombocytopenic states. Br J Haematol 1983; 54: 353-363
3 Myers TJ, Kim BK, Steiner M, Baldini MG. Platelet-associated complement C3 in immune thrombocytopenic purpura. Blood 1982; 59: 1023-1028
4 Nagaki K, Fujikawa K, Inai S. Studies on the fourth component of complement. II. The fourth component of complement in guinea pig and human platelets. Biken J 1965; 8: 129-141
5 Suba EA, Csako G. C1q (C1) receptor on human platelets: Inhibition of collagen-induced platelet aggregation by C1q (C1) molecules. J Immunol 1976; 117: 304-309
6 Taylor FB, Müller-Eberhard HJ. Qualitative description of factors involved in the retraction and lysis of dilute whole blood Clots and in the aggregation and retraction of platelets. J Clin Invest 1970; 49: 2068-2085
7 Winiarski J, Holm G. Platelet associated immunoglobulins and complement in idiopathic thrombocytopenic purpura. Clin Exp Immunol 1983; 53: 201-207
8 Endresen GK M, Førre Ø. Studies on the binding of immunoglobulins and immune complexes to the surface of human platelets: IgG molecules react with platelet Fc receptors with the CH₃ domain. Int Arch Allergy Appl Immunol 1982; 67: 33-39
9 Endresen GK M, Mellbye OJ. Studies on the binding of complement factor C3 to the surface of human blood platelets. Haemostasis 1984; 14: 269-280
10 Sandvik T, Endresen GK M, Førre Ø. Studies on the binding of complement factor C4 in human platelets. Int Arch Allergy Appl Immunol 1984; 74: 152-157
11 Veenhoven WA, van der Schans GS, Nieweg HO. Platelet antibodies in idiopathic thrombocytopenic purpura. Clin Exp Immunol. 1980 39. 645-651
12 Breckenridge RT, Rosenfeld SI, Graff KS, Leddy JP. Hereditary C5 deficiency in man. III. Studies of hemostasis and platelet responses to zymosan. J Immunol 1977; 118: 12-16
13 Martin SE, Breckenridge RT, Rosenfeld SI, Leddy JP. Responses of human platelets to immunologic stimuli: Independent roles for complement and IgG in zymosan activation. J Immunol 1978; 120: 9-14
14 Polley MJ, Nachman RL. The human complement system in thrombin-mediated platelet function. J Exp Med 1978; 147: 1713-1726
15 Polley MJ, Nachman RL. Human complement in thrombin-mediated platelet function. Uptake of the C5b-9 complex J Exp Med 1979; 150: 633-645
16 Zimmerman TS, Kolb WP. Human platelet-initiated formation and uptake of the C5-9 complex of human complement. J Clin Invest 1976; 57: 203-211
17 Henson PM, Spiegelberg HL. Release of serotonin from human platelets induced by aggregated immunoglobulins of different classes and subclasses. J Clin Invest 1973; 52: 1282-1288
18 Israels ED, Nisli G, Paraskevas F, Israels LG. Platelet Fc receptor as a mechanism for Ag-Ab complex-induced platelet injury. Thrombos Diathes Haemorrh 1973; 29: 434-444
19 Pfueller SL, Lüscher EF. The effects of aggregated immunoglobulins on human blood platelets in relation to their complement-fixing abilities. I. Studies of immunoglobulins of different types. J Immunol 1972; 109: 517-525
20 Wautier JL, Tobelem GM, Peltier AP, Caen JP. C1 and human platelets. II. Detection by immunological methods and role. Immunology 1976; 30: 459-465
21 Førre Ø, Michaelsen TE, Natvig JB. Antibody activity of heavy and light chains and recombined IgG of human IgG anti-D. Scand J Immunol 1976; 5: 155-160
22 Creighton WD, Lambert PH, Miescher PA. Detection of antibodies and soluble antigen-antibody complexes by precipitation with polyethylene glycol. J Immunol 1973; 111: 1219-1227
23 Endresen GK M. Immunological studies of plasma protease inhibitors associated with human blood platelets. Thromb Res 1980; 19: 157-163
24 Betterle C, Fabris F, De Marco L, Del Prete GF, Girolami A. Clotting factors and platelets. Haemostasis 1977; 6: 171-179
25 Coombs RR A, Bedford D. The A and B antigens on human platelets demonstrated by means of mixed erythrocyte-platelet agglutination. Vox Sang 1955; 5: 111-115
26 Evrin P-E, Pertoft H. β₂-microglobulin in human blood cells. J Immunol 1973; 111: 1147-1154
27 Flaum MA, Donlon JA, Gralnick HR, Rick ME. The identification and functional significance of factor VIII components on normal platelets. Thromb Res 1982; 26: 165-175
28 Tripodi D, Weis JW, Bonness PE, Pollack W. Identification of platelet orosomucoid. Transfusion 1971; 11: 139-144
29 Wautier JL, Souchon H, Cohen SolalL, Peltier AP, Caen JP. C1 and human platelets. III. Role of C1 subcomponents in platelet aggregation induced by aggregated IgG. Immunology 1976; 31: 595-599
30 Wenckel-Drake JD, Plow EF, Zimmerman TS, Painter RG, Ginsberg MH. Immunofluorescent localization of adhesive glycoproteins in resting and thrombin-stimulated platelets. Am J Pathol 1984; 115: 156-164
31 Nachman RL. Platelet proteins. In: The circulating platelet. Johnson SA. (Ed) Academic Press; New York: 1971. pp 207-224
32 Csako 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 SAβ₂ mG. Clin Exp Immunol 1979; 39: 461-469
33 Colman RW, Schreiber AD. Effect of heterologous antibody on human platelets. Blood 1976; 48: 119-131
34 Sarmay G, Sanderson A, Ivanyi J. Modulation of Fc receptors on human peripheral blood lymphocytes by antisera against β₂ microglobulin, Ia or immunoglobulin. Immunology 1979; 36: 339-345
35 Myllylä G. Aggregation of human blood platelets by unrelated antigen-antibody reaction: Sequence of reaction and role of complement. Ann Med Exp Biol Fenn 1973; 51: 11-21
36 Pfueller SL, Lüscher EF. The effects of aggregated immunoglobulins on human blood platelets in relation to their complement-fixing abilities. II. Structural requirements of the immunoglobulin. J Immunol 1972; 109: 526-533
37 Hutchinson RM, Davis P, Jayson MI V. Thrombocytosis in rheumatoid arthritis. Ann Rheum Dis 1976; 35: 138-142
38 Pfueller SL, Lüscher EF. The effects of immune complexes on blood platelets and their relationship to complement activation. Immunochemistry 1972; 9: 1151-1165
39 Weissbarth E, Baruth B, Mielke H, Liman W, Deicher H. Platelets as target cells in rheumatoid arthritis and systemic lupus erythematosus: A platelet specific immunoglobulin inducing the release reaction. Rheumatol Int 1982; 2: 67-73
40 McMillan R. Chronic idiopathic thrombocytopenic purpura. N Engl J Med 1981; 304: 1135-1147
41 Falus A, Merötey K, Bagdy D, Dioszegi M, Böhm U, Csak E, Bozsoky S. Beta₂-microglobulin-specific autoantibodies cause platelet aggregation and interfere with ADP-induced aggregation. Clin Exp Immunol 1982; 47: 103-109
42 Willis AL. Platelet aggregation mechanisms and their implications in haemostasis and inflammatory disease. In: Inflammation. Vane JR, Ferreira SH. (Eds) Springer; Germany: 1978. pp 138-205