HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jimmunol.0901019v1 183/4/2330    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Florey, O. Articles by Haskard, D. O. PubMed PubMed Citation Articles by Florey, O. Articles by Haskard, D. O.

Sphingosine 1-Phosphate Enhances Fc Receptor-Mediated Neutrophil Activation and Recruitment under Flow Conditions¹

British Heart Foundation Cardiovascular Medicine Unit, Imperial College, Hammersmith Hospital, London, United Kingdom

Sphingosine 1-phosphate (S1P) is a bioactive phospholipid that is released by platelets and endothelial cells and has been implicated in diverse biological functions. We hypothesized that S1P may influence immune complex-mediated polymorphonuclear neutrophil activation. Using flow cytometry and fluorescence spectrometry, we found that exogenous addition of S1P led to an enhanced polymorphonuclear neutrophil Fc receptor-mediated rise in intracellular Ca²⁺ and reactive oxygen species generation in a pertussis toxin-independent manner, while having only a small effect by itself. Thus, S1P amplifies a positive feedback loop where Fc receptor-mediated rises in Ca²⁺ and reactive oxygen species are interdependent, with reactive oxygen species acting to increase tyrosine phosphorylation and activity of upstream signaling intermediates. S1P augmentation of Fc receptor signaling translates to downstream functional consequences, including shape change and recruitment to endothelial surfaces coated with suboptimal levels of immune complexes. 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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by grants from the Wellcome Trust, British Heart Foundation, and Arthritis Research Campaign. We are also grateful for the support from the National Institute for Health Research Biomedical Research Centre funding scheme.

² Current address: Department of Pathology, Northwestern University, Chicago, IL 60611.

³ Address correspondence to Dr. Dorian Haskard, British Heart Foundation Cardiovascular Medicine Unit, Imperial College, Hammersmith Hospital, Du Cane Road, London W12 0NN, U.K. E-mail address: d.haskard{at}imperial.ac.uk

⁴ Abbreviations used in this paper: PMN, polymorphonuclear neutrophil; ROS, reactive oxygen species; S1P, sphingosine-1-phosphate; HAGG, heat-aggregated Ig; HMEC, human microvascular endothelial cell; IC, immune complex; GPCR, G protein-coupled receptor; NAC, N-acetylcysteine.