Platelets: Versatile modifiers of innate and adaptive immune responses to transplants

Purpose of Review: Over the last decade there has been mounting experimental data demonstrating that platelets contribute to acute vascular inflammation and atherosclerosis. This review focuses on recent findings that link platelets to inflammatory responses of relevance to transplants. Recent Findings: Although it has been known that platelets modify vascular inflammation by secretion of soluble mediators and release of microparticles, new aspects of these mechanisms are being defined. For example, platelet-derived CCL5 not only functions in homomers, but also forms more potent heteromers with platelet factor 4 (PF4; CXCL4). This heteromer formation can be inhibited with small molecules. New findings also demonstrate heterologous interactions of platelet microparticles with leukocytes that may increase their range of impact. By attaching to neutrophils, platelet microparticles appear to migrate out of blood vessels and into other compartments where they stimulate secretion of cytokines. Contact of platelets with extracellular matrix also can result in cleavage of hyaluronan into fragments that serve as an endogenous danger signal. Summary: Recent findings have expanded the range of interactions by which platelets can modify innate and adaptive immune responses to transplants.