Regulation of transendothelial permeability by Src Kinase

Transcellular transport of albumin from the endothelial lumen to the abluminal perivascular interstitium via caveolae is a primary determinant of basal endothelial permeability. Albumin binding to specific caveolae-associated proteins induces the internalization of caveolae from the endothelial plasma membrane. Albumin-containing caveolae detach from the plasma membrane and traffic to the opposite membrane where they release albumin into the extravascular space. The events initiating transcytosis have been shown to be tightly regulated by Src family kinases, and thus Src signaling is thought to be a critical switch regulating caveolae-mediated transcellular transport of the plasma protein albumin. Recently, accumulating evidence indicates the importance of caveolae-mediated albumin transport in endothelial hyperpermeability in response to inflammatory stimuli. In this review, we focus on the current understanding of Src signaling in regulating basal permeability and inflammation-evoked increase in transcellular albumin permeability of the pulmonary endothelium. (C) 2008 Elsevier Inc. All rights reserved.