Variability of Integrin α2β1 Activity on Human Platelets

Abstract

AbstractThe activity and surface antigenicity of α2β1on platelets from 27 normal subjects were found to vary significantly. A fourfold range of surface antigen correlates with a 20-fold variation in the ability of nonactivated, washed platelets to adhere to type I collagen and a fivefold variation in the adhesion of platelets to type III collagen. These differences in surface receptor are reflected in significant variation in the lag time required for type I collagen-induced platelet aggregation in platelet-rich plasma. Among the same individuals, no difference was observed in surface levels or activities of two other platelet integrins, the fibro-nectin receptor α2β1 and the fibrinogen receptor αIIbβ3. In all cases studied, we observed complimentary differences in the incorporation of 125l into surface α2β1. in quantity of surface α2β1 antigens, and in α2β1 collagen receptor activity. Despite variations in these parameters, there was no difference in the electrophoretic mobility or isoelectric point of either integrin subunit among the individuals studied. The wide range of activity and antigenicity of this platelet collagen receptor may result from polymorphism(s) in the α2β1 genes, or the activity of α2β1 may be variably regulated by another gene product. The heterogeneity of platelet α2β1 that we describe in this report certainly explains previous discrepancies concerning the contributions of this integrin to platelet adhesion to collagens. Most importantly, differences in surface collagen receptor activity may correlate with a long-term risk toward thrombosis, impaired hemostasis, and/or cardiovascular disease.