Platelets exit venules by a transcellular pathway at sites of F-Met peptide-induced acute inflammation in guinea pigs

Platelets maintain the integrity of vascular endothelium, but also appear outside of blood vessels in pathological states such as acute inflammation. However, it is widely believed that platelets extravasate from blood vessels only as the result of endothelial injury and that, on contacting extravascular collagen, they undergo a morphologically defined activation sequence and release their granule contents. We here report that platelets may cross intact venular endothelium without exhibiting this release reaction or injury. Platelets became adherent to the luminal surface of venular endothelium within similar to 15 min of intradermal injection of 10(-5) M N-formyl-methionyl-leucyl-phenylalanine in guinea pig flank skin. Individual intact platelets were noted in large endothelial cell cytoplasmic vacuoles from which they subsequently migrated abluminally. They then crossed the vascular basal lamina and entered the dermis without exhibiting evidence of a release reaction. Serial electron-microscopic sections confirmed that the cytoplasmic vacuoles within which platelets crossed endothelial cells were independent of interendothelial cell junctions which remained normally closed. Platelets extended pseudopods and gave other evidence of cell motility. These findings require a paradigm shift in our thinking about platelet movement and functions.