title: The interaction between C5a and sphingosine-1-phosphate in neutrophils for antineutrophil cytoplasmic antibody mediated activation.
abstract: BACKGROUND
  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.
authors.forename: Jian
authors.initials: J
authors.lastname: Hao
authors.forename: Yi-Min
authors.initials: YM
authors.lastname: Huang
authors.forename: Ming-Hui
authors.initials: MH
authors.lastname: Zhao
authors.forename: Min
authors.initials: M
authors.lastname: Chen
mesh_terms: D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000097:blood / Q000276:immunology*; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology*; D015936:Complement C5a / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008246:Lysophospholipids / Q000097:blood / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D018375:Neutrophil Activation / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000097:blood / Q000276:immunology
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D008246:Lysophospholipids; C060506:sphingosine 1-phosphate; D015936:Complement C5a; D013110:Sphingosine