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Sphingosine‐1‐phosphate (S1P) enhances Fcg receptor‐mediated neutrophil (PMN) recruitment under flow and reactive oxygen species (ROS) generation
Author(s) -
Florey Oliver,
Nourshargh Sussan,
Haskard Dorian
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.a634-d
Subject(s) - reactive oxygen species , microbiology and biotechnology , sphingosine 1 phosphate , chemistry , receptor , flow cytometry , platelet activation , sphingosine 1 phosphate receptor , intracellular , pertussis toxin , sphingosine , biochemistry , biology , platelet , immunology , g protein
Background S1P is a bioactive phospholipid released by platelets and endothelial cells that has been implicated in diverse biological functions. We hypothesized that S1P may influence immune‐complex‐mediated PMN activation. Methods and Results SIP (10μM) significantly augmented Fcγ receptor IIIb‐dependent PMN adhesion at 1.5 dynes/cm 2 to a substrate coated with sub‐optimal immune complexes (without S1P 22.78 ±1.5 cells/field of view, with S1P 33.25 ±3.2, p<0.03). Using fluorescence spectrometry, we found that exogenous addition of S1P led to an enhanced neutrophil Fcγ receptor‐mediated rise in intracellular Ca 2+ levels in a pertussis toxin‐independent manner, while inducing only a small Ca 2+ influx by itself. Reactive oxygen species (ROS) generation was also synergistically enhanced by S1P and Fcγ receptor co‐stimulation, as shown by flow cytometry with 123‐DHR. Inhibition of ROS generation abolished calcium flux and vice‐versa, as shown using n‐acetyl cysteine and EGTA respectively. Conclusions These data indicate that S1P augments neutrophil activation in response to Fc receptor ligation, with an interdependent signaling loop involving increased intracellular Ca 2+ levels and ROS generation. Taken together, S1P from activated platelets or endothelial cells may serve to amplify leukocyte recruitment and tissue injury at sites of immune complex deposition in vasculitis.