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Open Access Research article

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

Jian Hao12, Yi-Min Huang1, Ming-Hui Zhao1 and Min Chen1*

Author Affiliations

1 Renal Division, Department of Medicine, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Peking-Tsinghua Center for Life Sciences, Peking University, First Hospital, Peking University Institute of Nephrology, Beijing 100034, China

2 Renal Division, Department of Medicine, The Affiliated Hospital of Inner Mongolia Medical University, Huhehot, Inner Mongolia 010050, China

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Arthritis Research & Therapy 2014, 16:R142  doi:10.1186/ar4604

Published: 7 July 2014

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.