Effects of OKM5, a monoclonal antibody to glycoprotein IV, on platelet aggregation and thrombospondin surface expression.
The monoclonal antibody, OKM5, recognizes an 88-Kd monocyte membrane protein and also binds to the platelet membrane protein, GPIV (GPIIIb, CD36). In this study, we have found that the OKM5 target epitope is present at approximately 12,000 copies per platelet and that interaction with the antibody has both stimulatory and inhibitory effects on platelet function. In the absence of other stimuli, OKM5 induced platelet aggregation, secretion, and expression of fibrinogen receptors. These stimulatory responses required intact antibody as F(ab')2 fragments were not active but blocked the stimulatory activity of the intact antibody. In contrast, exposure of platelets to OKM5 followed by another strong stimulus such as thrombin resulted in a marked suppression of fibrinogen, fibronectin, and von Willebrand factor binding to the cells. This effect was not noted when a weak stimulus, adenosine diphosphate, was the second agonist. At OKM5 concentrations that interfered with fibrinogen binding to thrombin-stimulated platelets by 80% to 90%, platelet binding of exogenous thrombospondin, or surface expression of endogenous thrombospondin was not affected. The inhibitory effect of OKM5 on fibrinogen binding to thrombin-stimulated platelets was related to the formation of massive platelet aggregates in the samples. These results show that interaction of OKM5 with its target antigen on platelets can elicit diverse functional responses from the cells.
Aiken
M L
ML
Department of Biochemistry, University of Texas Health Science Center, Tyler.
Ginsberg
M H
MH
Byers-Ward
V
V
Plow
E F
EF
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D000943:Antigens, Differentiation / Q000276:immunology*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D018955:CD36 Antigens; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D010973:Platelet Adhesiveness / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects*; D010980:Platelet Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D019699:Thrombospondins; D014841:von Willebrand Factor / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D018955:CD36 Antigens; D010980:Platelet Membrane Glycoproteins; D019699:Thrombospondins; D014841:von Willebrand Factor; D005340:Fibrinogen