Molecular Basis of Leukocyte-Endothelium Interactions During the Inflammatory Response

The process of leukocyte extravasation, a critical step in the inflammatory response, involves the migration of leukocytes from the bloodstream towards target tissues, where they exert their effector function. Leukocyte extravasation is orchestrated by the combined action of cellular adhesion receptors and chemotactic factors, and involves radical morphological changes in both leukocytes and endothelial cells. Thus, it constitutes an active process for both cell types and promotes the rapid and efficient influx of leukocytes to inflammatory foci without compromising the integrity of the endothelial barrier. This article provides a review of leukocyte extravasation from both molecular and mechanical points of view, with a particular emphasis on the most recent findings on the topic. It includes a description of newly revealed steps in the adhesion cascade, such as slow rolling motion, intraluminal crawling and alternative pathways for transcellular migration, and discusses the functional role of novel adhesion receptors, the spatiotemporal organization of receptors at the plasma membrane and the signaling pathways that control different phases of the extravasation process.