Neutrophil adhesion and activation under flow

Alexander Zarbock, Klaus Ley, Alexander Zarbock, Klaus Ley

Abstract

Neutrophil recruitment into inflamed tissue in response to injury or infection is tightly regulated. Reduced neutrophil recruitment can result in a reduced ability to fight invading microorganisms. During inflammation, neutrophils roll along the endothelial wall of postcapillary venules and integrate inflammatory signals. Neutrophil activation by selectins and chemokines regulates integrin adhesiveness. Binding of activated integrins to their counter-receptors on endothelial cells induces neutrophil arrest and firm adhesion. Adherent neutrophils can be further activated to undergo cytoskeletal rearrangement, crawling, transmigration, superoxide production, and respiratory burst. Signaling through G-protein-coupled receptors, selectin ligands, Fc receptors and outside-in signaling through integrins are all involved in neutrophil activation, but their interplay in the multistep process of recruitment is only beginning to emerge. This review provides an overview of signaling in rolling and adherent neutrophils.

Figures

Figure 1. Two modes of neutrophil arrest:…
Figure 1. Two modes of neutrophil arrest: slow rolling versus immediate arrest
A. Neutrophils rolling on E-selectin pick up activating signals through PSGL-1 and Syk, resulting in partial activation of LFA-1 to the extended conformation with closed headpiece, indicated by the pink color. As soon as a neutrophil rolling on E-selectin encounters a surface with E-selectin and ICAM-1 (orange), the rolling velocity immediately decreases because LFA-1 now engages ICAM-1. This is schematically represented in the velocity trace on top. Even a small amount of a CXCR2 ligand such as immobilized CXCL1 (red) leads to arrest. B. Neutrophils rolling on P-selectin show little evidence of LFA-1 activation. Their rolling velocity changes little when ICAM-1 becomes available. A low dose of CXCL1 co-immobilized with P-selectin and ICAM-1 (P+I) cannot induce arrest, but a high dose can (red).

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