Platelet Activation through GPVI Receptor: Variability of the Response

Platelets are nuclear-free cell fragments responsible for preventing blood loss in case of the vascular wall injury. After a contact with collagen exposed when the vessel is damaged, platelets become activated through the receptor glycoprotein GPVI. This leads to platelet shape change, degranulation, aggregation, and procoagulant responses. The aim of this study was to detect changes in calcium mobilization and functional responses of platelets upon stimulation through the GPVI receptor. The study involved healthy adult volunteers and house mice Mus musculus of the C57B16 line (wild type). Calcium signaling was monitored by Fura-Red fluorophore's fluorescence using BD FACS Canto II flow cytometer. Integrin activation was observed either by platelets' binding of human fibrinogen or by Biola optical aggregometry. For the flow cytometry analysis, platelets were activated by collagen-related peptide CRP; when tested by aggregometry, platelets were activated using collagen. As a result of the study, the following phenomenon was revealed: in human platelets, significant inter-donor variability was detected in the relative change in the level of Ca2+ in the cytosol in response to stimulation; inter-donor variability in platelet integrin activation, shape change, and aggregation response was significantly less. In mice, such variability in the relative cytosolic calcium increase induced by stimulation was not observed. The observed variability of the calcium response of human platelets could be caused by differences in the GPVI expression or polymorphisms of the GPVI receptor gene in the studied donors. Similarities in the functional responses of platelets with different signaling patterns suggest a variable contribution of the phosphoinositide branch of the intracellular signaling in platelets in response to activation of GPVI.