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Arthritis Research & Therapy
Published in: Arthritis Research & Therapy 4/2014

Open Access 01-08-2014 | Research article

The interaction between C5a and sphingosine-1-phosphate in neutrophils for antineutrophil cytoplasmic antibody mediated activation

Authors: Jian Hao, Yi-Min Huang, Ming-Hui Zhao, Min Chen

Published in: Arthritis Research & Therapy | Issue 4/2014

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Abstract

Introduction

C5a plays an crucial role in antineutrophil cytoplasmic antibody (ANCA)-mediated neutrophil recruitment and activation. The current study further investigated the interaction between C5a and sphingosine-1-phosphate (S1P) in neutrophils for ANCA-mediated activation.

Methods

The plasma levels of S1P from 29 patients with ANCA-associated vasculitis (AAV) in active stage and in remission were tested by enzyme-linked immunosorbent assay (ELISA). The generation of S1P was tested in C5a-triggered neutrophils. The effect S1P receptor antagonist was tested on respiratory burst and degranulation of C5a-primed neutrophils activated with ANCA.

Results

The plasma level of circulating S1P was significantly higher in patients with AAV with active disease compared with patients in remission (2034.2 ± 438.5 versus 1489.3 ± 547.4 nmol/L, P < 0.001). S1P can prime neutrophils for ANCA-induced respiratory burst and degranulation. Compared with non-triggered neutrophils, the mean fluorescence intensity (MFI) value for CD88 expression was up-regulated significantly in S1P-triggered neutrophils. S1P receptor antagonist decreased oxygen radical production in C5a primed neutrophils induced by ANCA-positive IgG from patients. Blocking S1P inhibited C5a-primed neutrophil migration.

Conclusions

S1P triggered by C5a-primed neutrophils could further activate neutrophils. Blocking S1P could attenuate C5a-induced activation of neutrophils by ANCA. The interaction between S1P and C5a plays an important role in neutrophils for ANCA-mediated activation.
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Metadata
Title
The interaction between C5a and sphingosine-1-phosphate in neutrophils for antineutrophil cytoplasmic antibody mediated activation
Authors
Jian Hao
Yi-Min Huang
Ming-Hui Zhao
Min Chen
Publication date
01-08-2014
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 4/2014
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/ar4604

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