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Sphingosine‐1‐phosphate (S1P) attenuates acute inflammatory response to mediators platelet activating factor (PAF) and bradykinin (Bk)
Author(s) -
Ly J C,
Adamson R H,
Curry F E
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-d
Subject(s) - platelet activating factor , bradykinin , lipid signaling , sphingosine 1 phosphate , sphingosine , pharmacology , inflammatory response , platelet , chemistry , medicine , inflammation , receptor
Inhibition of Rac1 increases microvessel permeability (AJPHeart 286:H394, 2004). Activation of Rac1 inhibits acute hyperpermeability stimulated by PAF and enhances peripheral actin, and translocation of both actin‐binding protein VASP and the Rac1 dependent effector cortactin to cell‐cell junctions of endothelial monolayers. Here, we predicted that S1P would inhibit the response to mediators Bk and PAF. We determined hydraulic conductivity (L p ) of single post‐capillary venules of rat mesentery. Vessels were perfused with solution containing: 1) serum albumin (BSA, 10 mg/ml) in Ringer’s solution to establish control L p (25 min), 2) S1P (1 μM, 30 min), 3) S1P and PAF (10 nM, 30 min), 4) BSA (30 min), and 5) PAF without S1P (20 min). A second group of venules were tested for responsiveness to Bk (10 nM) using the same protocol. S1P significantly attenuated the response to PAF. Mean peak L p response (L p peak ) to PAF was 4.6 ± 0.9 × 10 −7 cm/(s×cmH 2 O) with S1P and was 13 ± 3.6 × 10 −7 cm/(s×cmH 2 O) without (p<0.05, n=6, Wilcoxon). Similarly, the mean L p peak to Bk was 7.6 ± 3.0 × 10 −7 cm/(s×cmH 2 O) with S1P and 26.4 ± 9.2 × 10‐7 cm/(s×cmH 2 O) without (p<0.05, n=11). A recent publication indicates very similar inhibitory action of S1P on PAF (AJPHeart 289:H840, 2005). Also, Rac1 activation via S1P is protective against lipopolysaccharide‐induced lung edema in mice (Cell Signal 17:131, 2005). The results are consistent with the hypothesis that Rac1 activation protects endothelium against acute inflammatory stimuli through stabilization of the peripheral actin‐cell adhesion complex. NIH HL28607