How platelets repair vascular injuries inflicted by infiltrating neutrophils. (A) Early platelet recruitment to the vessel wall during the cutaneous rpA, reaction as investigated by intravital microscopy. Platelets and neutrophils were stained in vivo, using fluorescent antibodies to GPIbβ (green color) and Ly-6G (red color). Single platelets were seen firmly adhering to the vessel wall and to neutrophils in areas of marked neutrophil margination and transmigration, which occurred in postcapillary venules. Scale bar, 100 µm. (B) Comparison of early platelet accumulation at the rpa site between control and thrombocytopenic wild-type mice and GPVI^−/− mice, as assessed by measurement of skin PF4 content. In wild-type mice, the rpA led to the recruitment of platelets, which was reduced in GPVI^−/− mice. Note that platelet recruitment to the inflamed skin was prevented by neutrophil depletion. Adapted from Gros et al.³⁴  (C) Schematic representation of how platelets can prevent bleeding from sites of neutrophil extravasation in postcapillary venules. (Left) Single platelets are recruited to the inflamed vessel walls through interactions with activated endothelial cells and neutrophils, and with the exposed basement membrane. Recruited platelets play a dual role by promoting edema formation (yellow arrows, 1) and amplifying neutrophil infiltration through the secretion of permeability factors and chemokines (eg, serotonin, vascular endothelial growth factor receptor, PF4, RANTES, SDF-1), while ensuring inflammatory hemostasis. Concomitantly with or subsequently to their pro-inflammatory effects, single platelets indeed prevent bleeding by filling gaps between endothelial cells and plugging breaches in the basement membrane caused by extravasating neutrophils (2). This protective action of platelets would notably involve interactions between GPVI and components of the exposed subendothelium (eg, laminin or collagen), and/or between CLEC-2 with podoplanin-expressing stromal cells in close proximity to blood vessels (eg, macrophages, fibroblasts). In addition to a mechanical action, platelets engaged by these pathways might also trigger vascoconstriction, bridge endothelial gaps (3), or promote closing of endothelial junctions (4) over holes in the basement membrane, through the secretion of antipermeability and endothelial cell survival factors (eg, S1P, angiopoietin-1, ADP, ATP). (Right) In case of more severe endothelial injury, as in models of cerebral ischemia-reperfusion, inflammatory hemostasis would rely on more classical mechanisms including GPIIb/IIIa-mediated platelet aggregation (5).