Proposed working model for the interaction between C5a and sphingosine-1-phosphate (S1P) in antineutrophil cytoplasmic antibody (ANCA)-mediated neutrophils activation. Neutrophils are primed by C5a to express ANCA antigens at the cell surface and supernatant. ANCA antibodies interact with the ANCA antigens which result in primed-neutrophil activation. The ANCA-activated neutrophils release S1P that can further activate neutrophils. S1P receptor antagonist may attenuate C5a-primed neutrophils for ANCA induced activation.