The lung endothelial αvβ3 integrin which is luminally located in lung capillaries, binds vitronectin-containing inflammatory products to increase capillary permeability (Circ. Res. 1995; 77:651-659). To determine signalling mechanisms, we determined cytosolic calcium concentration([Ca2+]i) by the fura method, in microvascular endothelial cells of rat lung (RLMEC). Vitronectin (400 μg/ml) increased [Ca2+]i of fura 2-loaded RLMEC by 176±30% from baseline of 92±14 nM, in 1 min and remained elevated for 5 min (P<.05; N=14). Immunoprecipitation of phospholipase Cγ (PLCγ) from RLMEC monolayers exposed to vitronectin, followed by immunoblotting with anti-phosphotyrosine(Bhattacharya, S., J. Biol. Chem. 1995; 270: 16781-87) revealed enhanced protein tyrosine phosphorylation (PtyrP) on PLCγ. Since activated PLCγ may increase inositol (1,4,5) triphosphate (IP3), we quantified IP3 by receptor-binding assay. In RLMEC monolayers, vitronectin treatment increased IP3 32±5% in 5 min (P<.05). We conclude, the signalling pathway induced by ligation of the lung endothleial αvβ3, sequentially consists of tyrosine phosphorylation of PLCγ, hence probable activation of PLCγ, release of IP3, then IP3-mediated increase of [Ca2+]i. Subsequently, increase of capillary permeability may be attributable to activation of Ca2+ dependent processes (HL54157, HL36024).
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Bhattacharya, S., Ying, X., Fu, C. et al. SIGNAL TRANSDUCTION BY AN INFLAMMATORY INTEGRIN IN LUNG ENDOTHELIAL CELLS.† 1467. Pediatr Res 41 (Suppl 4), 247 (1997). https://doi.org/10.1203/00006450-199704001-01486
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DOI: https://doi.org/10.1203/00006450-199704001-01486