Anti-myeloperoxidase antibodies enhance phagocytosis, IL-8 production, and glucose uptake of polymorphonuclear neutrophils rather than anti-proteinase 3 antibodies leading to activation-induced cell death of the neutrophils
Journal
Clinical rheumatology
Journal Volume
26
Journal Issue
2
Pages
216
Date Issued
2007-02
Author(s)
Abstract
Anti-neutrophil cytoplasmic antibodies (ANCA) not only are triggered by target protein myeloperoxidase (MPO) and proteinase 3 (PR3) of polymorphonuclear neutrophil (PMN) but also react with primed PMN to exert the inflammatory process in vasculitis syndrome. To clarify the crucial role of PMN in ANCA-associated vasculitis and the related mechanism, PMN was cultured with monoclonal antibody MPO-ANCA and PR3-ANCA to determine the function of phagocytosis, Interleukin- 8 (IL-8) production, glucose uptake, and TNF-related apoptosis induced ligand (TRAIL) production. The spontaneous membrane expression of MPO and PR3 on PMN could be significantly increased by lipopolysaccharide (LPS) and TNF-alpha, but not by IL-8 or GRO-alpha. The PMN-stimulating activity of ANCA was demonstrated by enhancing phagocytosis, IL-8 production, and glucose uptake that was more prominent by MPO-ANCA. The PMN stimulation by ANCA was not through protein kinase, H2O2, or superoxide anion radicals as their inhibitors exerted no effect on ANCA-mediated activation. On the other hand, ANCA also accelerated PMN apoptosis and increased TRAIL production. These results demonstrate that activation-induced cell death (AICD) mechanism could be initiated in PMN with existence of ANCA. In conclusion, MPO-ANCA is more potent in stimulating PMN than PR3-ANCA. ANCA-activated PMN is not only responsible for the amplified inflammatory process in blood vessel but also initiates immune circuit via triggered macrophage/monocyte by apoptotic PMN through the mechanism of AICD elicited by ANCA.
Subjects
activation-induced cell death; anti-neutrophil cytoplasmic autoantibody; myeloperoxidase; polymorphonuclear neutrophil; proteinase-3; ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES; TUMOR-NECROSIS-FACTOR; WEGENERS-GRANULOMATOSIS; SYSTEMIC VASCULITIS; APOPTOTIC NEUTROPHILS; ENDOTHELIAL-CELLS; DISEASE-ACTIVITY; FACTOR-ALPHA; T-CELLS; AUTOANTIBODIES
Publisher
SPRINGER LONDON LTD
Type
journal article