Variability of integrin alpha 2 beta 1 activity on human platelets

Abstract

The activity and surface antigenicity of alpha 2 beta 1 on 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 fibronectin receptor alpha 5 beta 1 and the fibrinogen receptor alpha IIb beta 3. In all cases studied, we observed complimentary differences in the incorporation of 125I into surface alpha 2 beta 1, in quantity of surface alpha 2 beta 1 antigens, and in alpha 2 beta 1 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 alpha 2 beta 1 genes, or the activity of alpha 2 beta 1 may be variably regulated by another gene product. The heterogeneity of platelet alpha 2 beta 1 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.

Longitudinal Serum Proteome Characterization of COVID-19 Patients With Different Severities Revealed Potential Therapeutic Strategies

“…Compared with other clusters, the levels of proteins involved in the ECM-receptor interaction pathway, as well as immunoglobulin and receptors, markedly declined in C3 ( Figure 4B ). Integrin α2β1 induces platelet aggregation by mediating adhesion of platelets to different collagens ( 26 ). Declines of integrin ITGB1, proteins promoting the formation of platelet plugs (GP1BA, THBS1, GP5, and DAG1), and extracellular matrix proteins (COL1A1, COL6A1, COL6A3, and TNC) ( Table S3 ) indicated decreased platelet aggregation in cluster C3.…”

Association of ITGA2 Dual Site Variants with Recurrent Ischemic Events in Patients Undergoing Stenting for Symptomatic Intracranial Atherosclerotic StenosisAuthor list

“…These connections trigger potent signaling cascades culminating in thrombosis. Existing literature reveals that platelet surface α2b1 levels correlate with the adhesive capacity and extent of platelets to collagen in the bloodstream [19]. A de cit in GP Ia/IIa, either congenital or acquired, can precipitate hemorrhagic tendencies, with SNPs in the ITAG2 gene modulating the expression of GP Ia/IIa [20].…”