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Originally published online as doi:10.2353/ajpath.2008.070502 on December 13, 2007

Published online before print December 13, 2007
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(American Journal of Pathology. 2008;172:1-7.)
© 2008 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2008.070502

Biological Perspectives

Mechanisms and Consequences of Neutrophil Interaction with the Endothelium

Alexander Zarbock*{dagger} and Klaus Ley*{ddagger}§

From the Robert M. Berne Cardiovascular Research Center,*Department of Physiology and Biological Physics,{ddagger}Biomedical Engineering,§University of Virginia; Charlottesville, Virginia; and the Department of Anesthesiology and Intensive Care Medicine,{dagger}University of Münster, Münster, Germany

Abstract

Leukocyte recruitment into inflamed tissue proceeds in a cascade-like fashion. The first contact of neutrophils with the endothelium is mediated by selectins and their counterreceptors, followed by rolling of neutrophils along the endothelial wall of postcapillary venules and integrin-mediated arrest. While rolling, neutrophils collect different inflammatory signals that can activate several pathways. In addition to activation of neutrophils by ligation of G-protein-coupled receptors with chemokines and other chemoattractants, integrins and selectin ligands are also able to signal into the cell, where they initiate neutrophil extravasation, promote cytoskeletal rearrangement, and ultimately induce superoxide production and degranulation. These signaling pathways may be targeted by therapeutic interventions to inhibit specific functions of neutrophils without affecting others. This Review is focused on the signaling events during the interaction of neutrophils with the endothelium.




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