Alloantibody induced platelet responses in transplants: Potent mediators in small packages

The early histological studies of organ allografts noted platelets attached to vascular endothelium. Platelets adhere to vessels before any morphological evidence of endothelial injury. Subsequently, in vitro and in vivo experiments have demonstrated that alloantibodies can induce exocytosis of von Willebrand factor and P-selectin from endothelial cells and attachment of platelets within minutes. Platelets also adhere to and stimulate leukocytes. These interactions are increased by complement activation. After attachment platelets degranulate, releasing preformed mediators. Some chemokines stored together in platelet granules can form heteromers with synergistic functions. Heteromers containing platelet factor 4 (PF4; CXCL4) are specific to platelets and provide insights to unique platelet functions and opportunities for therapeutic intervention.