Neutrophil and platelet recruitment and activation into inflamed organs play key roles in the acute inflammatory response. Leukocyte recruitment is initiated by interactions with endothelial selectins, followed by activation of integrins which interact with their counter-receptors on the inflamed endothelium. Before migrating into the surrounding tissue, neutrophils actively crawl on the inflamed endothelium displaying a characteristic polarization with distinct microdomains at the leading (LE) and trailing edges (TE). During this period, they establish frequent interactions with circulating erythrocytes through the LE, which in the context of sickle cell disease can lead to vascular occlusion (Turhan et al., P.N.A.S. 2002 and unpublished data). During high-speed multichannel fluorescence intravital microscopy (MFIM) experiments, we have noted that neutrophils (identified by CD45+ Gr-1+ F4/80- expression) crawling on the inflamed endothelium actively interact with circulating platelets (identified in vivo by CD41 expression). In conditions in which inflammation was induced by surgical trauma only, platelet interactions were relatively rare and mediated by both the TE (identified in vivo by L-selectin clustering) and LE (opposite to L-selectin clusters). By contrast, in venules inflamed by the administration of TNFα, platelet interactions with the LE of crawling neutrophils were markedly increased. We have previously reported (
Disclosures: No relevant conflicts of interest to declare.