Journal Article

How leukocytes cross the vascular endothelium

Vestweber, Dietmar

2015

Overview

Key Points Immune responses depend on the ability of leukocytes to move from the circulation into tissues. Leukocyte extravasation is guided and controlled by endothelial cells that capture circulating leukocytes and open a path for diapedesis. Regulation of integrin-mediated adhesion controls the slowing down of leukocyte rolling, leukocyte arrest, crawling and migration through the blood vessel wall. Each of these cellular functions is tightly regulated and depends on different extracellular factors and binding partners with varying signalling requirements. A central step in the diapedesis process involves a mechanism that stimulates the opening of endothelial cell junctions, which depends on regulating the function of VE-cadherin. An alternative, although less common, pathway is the transcellular route through endothelial cells. The diapedesis process involves many functions of leukocytes and endothelial cells, from stopping intraluminal crawling at suitable exit sites to loosening of endothelial cell contacts, preventing plasma leakage, extending the membrane surface area at endothelial cell junctions, active leukocyte migration through the junctional cleft, preventing reverse transmigration and sealing of the junction after diapedesis. After crossing the endothelial barrier, leukocytes crawl along pericytes to reach preferential sites of exit through the basement membrane that are characterized by low levels of expression of certain protein components. Understanding the process of leukocyte diapedesis in more detail will help to identify molecular targets, to interfere with various inflammatory processes. Reciprocal interactions between leukocytes and endothelial cells enable leukocytes to recognize the blood vessel endothelium in areas of inflammation and transmigrate across the endothelial barrier to mount an immune response in infected and/or damaged tissues. Immune responses depend on the ability of leukocytes to move from the circulation into tissue. This is enabled by mechanisms that guide leukocytes to the right exit sites and allow them to cross the barrier of the blood vessel wall. This process is regulated by a concerted action between endothelial cells and leukocytes, whereby endothelial cells activate leukocytes and direct them to extravasation sites, and leukocytes in turn instruct endothelial cells to open a path for transmigration. This Review focuses on recently described mechanisms that control and open exit routes for leukocytes through the endothelial barrier.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 12E7 Antigen / 631/250/254 / 631/250/256 / 631/80/79 / 631/80/84 / Animals / Antigens, CD - physiology / Biomedicine / Cell Adhesion Molecules - physiology / Cell Movement / Endothelium / Endothelium, Vascular - physiology / Humans / Immunology / Integrins - physiology / Intercellular Adhesion Molecule-1 - physiology / Leukocytes / Leukocytes - physiology / Physiological aspects / review-article