Variation in human platelet glycoprotein VI content modulates glycoprotein VI-specific prothrombinase activity.
- Glycoprotein VI (GPVI) is a platelet-specific receptor for collagen that figures prominently in signal transduction. An addition to binding to type I and III collagens, GPVI is also bound specifically by collagen-related peptide and convulxin (CVX), a snake venom protein. We developed a quantitative assay of platelet GPVI in which biotin-conjugated CVX binds selectively to GPVI in separated total platelet proteins by a ligand blot procedure. Using this approach, we have documented a 5-fold range in platelet GPVI content among 23 normal healthy subjects. In addition, we have determined that CVX-induced or collagen-related peptide-induced prothrombinase activity is directly proportional to the platelet content of GPVI. A statistically significant correlation was observed at 2 CVX concentrations: 14.7 ng/mL (R(2)=0.854 and P<0.001, n=11) and 22 ng/mL (R(2)=0.776 and P<0.001, n=12). In previous studies, we established a similar range of expression of the integrin collagen receptor alpha(2)beta(1) on platelets of normal subjects. Among 15 donors, there is a direct correlation between platelet alpha(2)beta(1) density and GPVI content (R(2)=0.475 and P=0.004). In view of the well-documented association of GPVI with platelet procoagulant activity, this study suggests that the variation in GPVI content is a potential risk factor that may predispose individuals to hemorrhagic or thromboembolic disorders.
Furihata
K
K
Roon Research Center for Arteriosclerosis and Thrombosis, Division of Experimental Hemostasis and Thrombosis, The Scripps Research Institute, La Jolla, California, USA.
Clemetson
K J
KJ
Deguchi
H
H
Kunicki
T J
TJ
D001792:Blood Platelets / Q000737:chemistry* / Q000201:enzymology*; D003435:Crotalid Venoms / Q000378:metabolism / Q000494:pharmacology; D018076:DNA, Complementary; D004591:Electrophoresis, Polyacrylamide Gel; D006470:Hemorrhage / Q000209:etiology; D006801:Humans; D016023:Integrins / Q000378:metabolism; D037181:Lectins, C-Type; D015539:Platelet Activation / Q000187:drug effects; D010980:Platelet Membrane Glycoproteins / Q000032:analysis* / Q000235:genetics / Q000502:physiology*; D038981:Receptors, Collagen; D013925:Thromboplastin / Q000378:metabolism*; D013927:Thrombosis / Q000209:etiology
D003435:Crotalid Venoms; D018076:DNA, Complementary; D016023:Integrins; D037181:Lectins, C-Type; D010980:Platelet Membrane Glycoproteins; D038981:Receptors, Collagen; C098341:platelet membrane glycoprotein VI; C028890:convulxin; D013925:Thromboplastin