Platelet glycoprotein VI modulates leukocyte characteristics in sepsis-induced systemic inflammatory response in male mice.

Platelets are responsible for maintaining vascular integrity through the process of hemostasis with glycoprotein VI (GPVI) acting as a major receptor for platelet activation. Interestingly, platelet participation in inflammation is an evolving concept with few studies exploring GPVI in the framework of inflammation and even less in the context of the most severe inflammatory condition: sepsis. Here we utilized a GPVI deficient mouse model (GPVI-/-) to elucidate the role of GPVI in the formation of circulating platelet-leukocyte aggregates (PLAs) and how GPVI driven modifications impact leukocyte phenotype and function under septic systemic inflammatory conditions. Using the cecal ligation and puncture (CLP) technique to model sepsis in male mice, we report GPVI-mediated modification of several inflammatory characteristics. GPVI deficiency reduced platelet adhesion to neutrophils and monocytes during sepsis, resulting in reduced neutrophil and increased monocyte activation. Furthermore, monocytes exhibited altered polarization with GPVI deletion, raising the levels of circulating non-classical monocytes. The loss of GPVI also elicited a significant reduction in the levels of circulating TNFα. Finally, sepsis-induced mortality was significantly exacerbated as survival was dramatically reduced in GPVI-/- mice over a five-day period. These findings suggest that platelet GPVI impacts the inflammatory response during sepsis in a previously undocumented manner.