Variability of integrin alpha 2 beta 1 activity on human platelets.
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.
Kunicki
T J
TJ
Blood Research Institute, Blood Center of Southeastern Wisconsin, Milwaukee.
Orchekowski
R
R
Annis
D
D
Honda
Y
Y
D000595:Amino Acid Sequence; D000818:Animals; D001792:Blood Platelets / Q000737:chemistry*; D003094:Collagen / Q000494:pharmacology; D005260:Female; D006801:Humans; D016023:Integrins / Q000032:analysis* / Q000502:physiology; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D010973:Platelet Adhesiveness; D010974:Platelet Aggregation; D010980:Platelet Membrane Glycoproteins / Q000032:analysis; D038981:Receptors, Collagen; D017469:Receptors, Fibronectin / Q000032:analysis
D016023:Integrins; D010980:Platelet Membrane Glycoproteins; D038981:Receptors, Collagen; D017469:Receptors, Fibronectin; D003094:Collagen