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Tyrosine Phosphorylation and Barrier Dysfunction in Pulmonary Microvascular Endothelial Cells During Burn Plasma Stimulation
Author(s) -
Guo Mingzhang,
Breslin Jerome W.,
Reynoso Rashell,
Sun Hengrui,
Wu Mack H.,
Yuan Sarah Y.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a707-a
Subject(s) - adherens junction , phosphorylation , tyrosine phosphorylation , ve cadherin , barrier function , tyrosine kinase , endothelial dysfunction , endothelial stem cell , medicine , tyrosine , tight junction , microbiology and biotechnology , cancer research , chemistry , biology , endocrinology , cadherin , signal transduction , biochemistry , cell , in vitro
Microvascular leakage has been implicated in the pathogenesis of multiple organ failure including ARDS in trauma and thermal injury. To date, the precise mechanisms underlying burn‐induced lung vascular endothelial barrier dysfunction are not fully understood. The aim of this study was to examine the changes in endothelial adherens junctions and barrier function under burn‐related conditions. Rat pulmonary microvascular endothelial cells were treated with fresh plasma derived from rats subjected to 25% 3rd‐degree burns. The burn plasma induced a significant tyrosine phosphorylation in β‐catenin, accompanied by a decrease in the association of VE‐cadherin with β‐catenin, indicative of adherens junction disorganization. The changes in the junctional proteins occurred concomitantly with an impaired endothelial barrier function, as evidenced by a decrease in the transendothelial electric resistance. Pharmacological inhibition of Src kinase activity attenuated β‐catenin tyrosine phosphorylation and the hyperpermeability response to burn plasma. The results suggest that tyrosine phosphorylation‐associated endothelial adherens junction disorganization may be involved in the mechanisms underlying burn‐induced barrier dysfunction in the lung. Supported by NHLBI grants HL‐61507, HL‐70752 and HL‐73324.