Determinants of neutrophil migration

This figure illustrates circulating neutrophil interactions with vascular endothelial cells during recruitment to sites of infection or inflammation. At left, neutrophils (PMNs) and endothelial cells are represented in their basal states prior to exposure of either cell type to inflammatory mediators. Constitutive ICAM-2 is expressed on endothelial cells and does not affect free-flowing PMN, which constitutively express L-selectin and its ligand SleX. The adjacent right section illustrates PMN rolling onto endothelial cells, which express E-selectin after activation by IL-1, TNF-alpha, or endotoxin. E-selectin induces attachment of PMN to endothelial cells, mediated by the L- selectin ligand SleX. Endothelial cells release IL-8, GM-CSF and PAF, while other chemoattractants may also be sensed by rolling PMN. One or more of these molecules induce PMN to express beta-2 integrin Mac 1 (and LFA-1, not shown) which mediates firm adherence of PMN to ICAM-1 expressed by activated endothelial cells. At right, PMN is illustrated crawling along endothelial cells and squeezing between them, aided by endothelial cell PECAM-1, which binds PMN Mac-1. The sub-endothelial basement membrane is eroded, presumably by secretion of PMN gelatinase B and elastase.