Expression of the Drug-Dependent Antigen for Quinine-Dependent Antiplatelet Antibodies on GP III a but not that on GPI b, II b or IX on Human Endothelial Cells

Summary

In quinine- and quinidine-induced thrombocytopenic purpura IgG antibodies are known to react in a drug-dependent manner with different combinations of surface glycoproteins (GP) Ib , IIb, IIIa and IX. Because endothelial cells share a number of properties of platelets, including the presence of GP Ilia and GPIb-like proteins, we have compared these two cell types for their quinine-dependent IgG binding abilities. By immunoblotting of endothelial cells, quinine-dependent IgG binding from four patient sera was observed only to a 93 kDa component corresponding to GP Ilia. Strong IgG binding independent of the drug was found at 170–180 kDa. Thus endothelial cells express the GP Ilia quinine-dependent epitope on platelet GP IIIa , but not those on other platelet glycoproteins.

• References

• 1 Kunicki TJ, Johnson MM, Aster RA. Absence of the platelet receptor for drug-dependent antibodies in the Bernard-Soulier syndrome. J Clin Invest 1978; 62: 716-719
• 2 Chong BH, Berndt MC, Koutts J, Castaldi P. Quinidine-induced thrombocytopenia and leukopenia: demonstration and characterisation of distinct antiplatelet and antileukocyte antibodies. Blood 1983; 62: 1218-1223
• 3 Pfueller SL, Bilston RA, Logan D, Gibson JM, Firkin BG. Heterogeneity of drug-dependent platelet antigens and their antibodies in quinine- and quinidine-induced thrombocytopenia: Involvement of glycopoteins Ib , II b, Ilia and IX. Blood 1988; 72: 1155-1162
• 4 Jaffe EA, Hoyer LW, Nachman RL. Synthesis of antihemophilic factor antigen by cultured human endothelial cells. J Clin Invest 1973; 52: 2757-2764
• 5 Jaffe EA, Mosher DF. Synthesis of fibronectin by cultured human endothelial cells. J Exp Med 1978; 147: 1779-1791
• 6 Awbrey BJ, Hoak JC, Owen WG. Binding of human thrombin to cultured human endothelial cells. J Biol Chem 1979; 254: 4092-4095
• 7 Rodgers GM, Shuman MA. Prothrombin is activated on vascular endothelial cells by Factor Xa and calcium. Proc Natl Acad Sci 1983; 80: 7001-7005
• 8 Rimon S, Melamed R, Savion N, Scott T, Nawroth PP, Stern DM. Identification of a factor IX/IXa binding protein on the endothelial cell surface. J Biol Chem 1987; 262: 6023-6031
• 9 Maruyama I, Salem HH, Majerus PW. Coagulation Factor Va binds to human umbilical vein endothelial cells and accelerates Protein C activation. J Clin Invest 1984; 74: 224-230
• 10 Dejana E, Languino LR, Polentarutti N, Balconi G, Ryckewaert JJ, Larrieu MJ, Donati MB, Mantovani A, Marguerie G. Interaction between fibrinogen and cultured endothelial cells. Induction of migration and specific binding. J Clin Invest 1985; 75: 11-18
• 11 Fitzgerald LA, Charo IF, Phillips DR. Human and bovine endothelial cells synthesize membrane proteins similar to human platelet glycoproteins IIb and Ilia. J Biol Chem 1985; 260: 10893-10896
• 12 Leeksma OC, Zandbergen-Spaargaren J, Giltay JC, van Mourik JA. Cultured human endothelial cells synthesize a plasma membrane protein complex immunologically related to the platelet glycoprotein IIb/IIIa complex. Blood 1986; 67: 1176-1180
• 13 Newman PJ, Kawai Y, Montgomery RR, Kunicki TJ. Synthesis by cultured human umbilical vein endothelial cells of two proteins structurally and immunologically related to platelet membrane glycoproteins IIb and IIIa. J Cell Biol 1986; 103: 81-86
• 14 Fitzgerald LA, Steiner B, Rail SC, Lo SS, Phillips DR. Protein sequence of endothelial glycoprotein Ilia derived from a cDNA clone. Identity with platelet glycoprotein IIIa and similarity to “integrin”. J Biol Chem 1987; 262: 3936-3939
• 15 Leeksma OC, Giltay JC, Zandbergen-Spaagaren J, Modderman PW, van Mourik JA, von dem Borne A EG K. The platelet alloantigen Zw^a or PI^AI is expressed by cultured endothelial cells. Brit J Haematol 1987; 66: 369-373
• 16 Sprandio JD, Shapiro SS, Thiagarajan P, McCord S. Cultured human umbilical vein endothelial cells contain a membrane glycoprotein immunologically related to platelet glycoprotein Ib. Blood 1988; 71: 234-237
• 17 Asch AS, Fujimoto M, Adelman B, Nachman RL. An endothelial cell glycoprotein lb like molecule mediates von Willebrand factor binding. Circulation 1986; 74: 232
• 18 Pfueller SL, Firkin BG, McGrath KM, Logan D. Analysis of immunoglobulins that bind to platelets from serum of patients with immune thrombocytopenia: molecular weight distribution. Thromb Res 1987; 47: 305-314
• 19 Jaffe EA, Nachman RL, Becker CG, Minick CR. Cultures of human endothelial cells derived from umbilical veins. Identification by morphological and immunological criteria. J Clin Invest 1973; 52: 2745-2756
• 20 Smith RL, Griffin CA. Separation of plasma fibronectin from associated hemagglutinating activity by elution from gelatin-agarose at pH 5.5. Thromb Res 1985; 37: 91-101
• 21 Ginsberg MH, Loftus J, Ryckwaert J, Pierschbacher M, Pytela R, Ruoslahti E, Plow EF. Immunochemical and amino-terminal sequence comparison of two cytoadhesins indicates they contain similar or identical B subunits and distinct a subunits. J Biol Chem 1987; 262: 5437-5440
• 22 Pfueller SL, Logan D, Tran TT, Bilston RA. Naturally occurring IgG antibodies to intracellular and cytoskeletal components of human platelets. Clin Exp Immunol 1989 In Press