Proposed mechanism for platelet GPVI in maintaining vascular integrity during immune-complex–mediated inflammation. (A) Proposed mechanism for the role of platelets in wild-type (WT) mice. (A1) Immune complex formation in the perivascular compartment induces endothelial cells activation mainly through the release of proinflammatory cytokines and histamine from activated immune cells. (A2) Neutrophils are recruited to the activated endothelium, adhere, and transmigrate to the inflamed tissue. (A3,4) Platelets, including activation of GPVI, enhance neutrophil recruitment, infiltration, degranulation, and oxidative stress. (A5) Single platelets adhere to the subendothelium and seal the neutrophil-mediated vascular damage. (B) Proposed mechanism for the role of platelets in GPVI^−/− mice. (B4) Neutrophil recruitment, infiltration, and degranulation in the inflamed tissue induce vascular damage, although this is partly reduced by the absence of GPVI. (B5) Platelets are not able to adhere and seal neutrophil-mediated vascular damage in the absence of GPVI, thereby increasing blood leakage and local hemorrhage. IC, immune complex; ROS, reactive oxygen species; TNF, tumor necrosis factor; IL8, interleukin-8; IgG, immunoglobulin G.