title: Neutrophil transmigration, focal adhesion kinase and endothelial barrier function.
abstract: Neutrophil activation is an essential component of innate immune defense against infection and injury. In response to inflammatory stimulation, circulating neutrophils undergo a series of dynamic and metabolic changes characterized by β2-intergrin mediated adhesion to microvascular endothelium and subsequent transendothelial migration. During this process, neutrophils release granular contents containing digestive enzymes and produce cytotoxic agents such as reactive oxygen species and cytokines. These products target endothelial barriers inducing phosphorylation-triggered junction dissociation, actin stress fiber formation, and actomyosin contraction, manifest as paracellular hyperpermeability. Endothelial cell-matrix focal adhesions play an integral role in this process by providing structural support for endothelial conformational changes that facilitate neutrophil transmigration, as well as by recruiting intracellular molecules that constitute the hyperpermeability signaling cascades. As a central connector of the complex signaling network, focal adhesion kinase (FAK) is activated following neutrophil adhesion, and further mediates the reorganization of endothelial integrin-matrix attachments in a pattern coordinating with cytoskeleton contraction and junction opening. In this review, we present recent experimental evidence supporting the importance of FAK in neutrophil-dependent regulation of endothelial permeability. The discussion focuses on the mechanisms by which neutrophils activate FAK and its downstream effects on endothelial barriers.
authors.affiliation: Division of Research, Department of Surgery, University of California at Davis School of Medicine, Sacramento, CA 95817, USA.
authors.forename: Sarah Y
authors.initials: SY
authors.lastname: Yuan
authors.forename: Qiang
authors.initials: Q
authors.lastname: Shen
authors.forename: Robert R
authors.initials: RR
authors.lastname: Rigor
authors.forename: Mack H
authors.initials: MH
authors.lastname: Wu
mesh_terms: D000818:Animals; D002199:Capillary Permeability; D002448:Cell Adhesion; D042783:Endothelial Cells / Q000201:enzymology* / Q000276:immunology; D004789:Enzyme Activation; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D022001:Focal Adhesions / Q000201:enzymology* / Q000276:immunology; D006801:Humans; D018375:Neutrophil Activation; D009504:Neutrophils / Q000201:enzymology* / Q000276:immunology; D015398:Signal Transduction; D057705:Transendothelial and Transepithelial Migration
chemical_list: D051416:Focal Adhesion Protein-Tyrosine Kinases