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Sphingosine 1‐phosphate (S1P) prevents platelet activating factor (PAF)‐induced vascular leakage through its inhibitory action on endothelial gap formation
Author(s) -
He Pingnian,
Jiang Yanyan,
Wen Ke
Publication year - 2007
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.21.5.a489
Subject(s) - microvessel , platelet activating factor , vascular permeability , chemistry , biophysics , permeability (electromagnetism) , blood vessel , endothelium , perfusion , anatomy , angiogenesis , biochemistry , biology , endocrinology , medicine , membrane
Our previous study demonstrated that S1P, a native blood born lipid, prevents PAF‐induced permeability increase (AJP 289 :, 2005). This study aims to investigate the underlying mechanisms of its protective effect. Red fluorescence microsphere (FM, 100 nm) was used as tracer to mark PAF‐induced vascular leakage in individually perfused venular microvessels in rat mesenteries. Stacks of successive X‐Y confocal images were acquired and reconstructed to illustrate three‐dimensional accumulation of FM in intact microvessel walls. Total fluorescence intensity per unit area of vessel wall, FI/A, was used to quantify FM accumulation. Perfusion of microvessels with FM for 10 min resulted in a thin uniformed layer of red fluorescence in the vessel wall under control conditions. FI/A increased to 10.2±2.3 times of the control 10 min after each vessel was exposed to PAF (10 nM, n=5). The accumulated FM was preferentially located at endothelial cell (EC) clefts, indicating EC gap formation. Pre‐perfusing mivrovessels with S1P (10 μM) for 30 min significantly attenuated PAF‐induced FM accumulation at EC clefts and FI/A was reduced to 1.9±0.4 times the control value (n=4). This newly established method allows a three‐dimensional visualization and quantification of PAF‐induced vascular leakage in intact microvessels. Our results provided the first direct evidence in intact microvessels that the inhibitory effect of S1P on PAF‐induced increases in microvessel permeability was through its inhibitory action on EC gap formation. Supported by AHA GIA and NIH HL56237.