Journal
CHEMICO-BIOLOGICAL INTERACTIONS
Volume 171, Issue 2, Pages 177-189Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.cbi.2007.08.006
Keywords
Src tyrosine kinases; endothelium; vascular permeability; inflammation; drug delivery; caveolae
Funding
- NHLBI NIH HHS [R01 HL071626-05A1, P01 HL060678-080005, P01 HL060678, R01 HL071626-04, HL71626, R01 HL071626, HL60678] Funding Source: Medline
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An important function of the endothelium is to regulate the transport of liquid and solutes across the semi-permeable vascular endothelial barrier. Two cellular pathways have been identified controlling endothelial barrier function. The normally restrictive paracellular path way, which can become leaky during inflammation when gaps are induced between endothelial cells at the level of adherens and tight junctional complexes, and the transcellular pathway, which transports plasma proteins the size of albumin via transcytosis in vesicle carriers originating from cell surface caveolae. During non-inflammatory conditions, caveolae-mediated transport may be the primary mechanism of vascular permeability regulation of fluid phase molecules as well as lipids, hormones, and peptides that bind avidly to albumin. Src family protein tyrosine kinases have been implicated in the upstream signaling pathways that lead to endothelial hyperpermeability through both the paracellular and transcellular pathways. Endothelial barrier dysfunction not only affects vascular homeostasis and cell metabolism, but also governs drug delivery to underlying cells and tissues. In this review of the field, we discuss the current understanding of Src signaling in regulating paracellular and transcellular endothelial permeability pathways and effects on endogenous macromolecule and drug delivery. (c) 2007 Elsevier Ireland Ltd. All rights reserved.
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