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

Clin Rheumatol. 2007 Feb;26(2):216-24. doi: 10.1007/s10067-006-0285-3. Epub 2006 Mar 31.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Antineutrophil Cytoplasmic / pharmacology*
  • Antibodies, Monoclonal / pharmacology
  • Apoptosis / drug effects*
  • Cells, Cultured
  • Chemokine CXCL1
  • Chemokines, CXC / pharmacology
  • Drug Combinations
  • Flow Cytometry
  • Glucose / metabolism
  • Humans
  • Interleukin-8 / metabolism*
  • Interleukin-8 / pharmacology
  • Lipopolysaccharides / pharmacology
  • Myeloblastin / immunology*
  • Myeloblastin / metabolism
  • Neutrophil Activation / drug effects
  • Neutrophils / drug effects*
  • Neutrophils / metabolism
  • Peroxidase / immunology*
  • Peroxidase / metabolism
  • Phagocytosis / drug effects*
  • TNF-Related Apoptosis-Inducing Ligand / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology


  • Antibodies, Antineutrophil Cytoplasmic
  • Antibodies, Monoclonal
  • CXCL1 protein, human
  • Chemokine CXCL1
  • Chemokines, CXC
  • Drug Combinations
  • Interleukin-8
  • Lipopolysaccharides
  • TNF-Related Apoptosis-Inducing Ligand
  • Tumor Necrosis Factor-alpha
  • Peroxidase
  • Myeloblastin
  • Glucose