MPO-ANCA induces IL-17 production by activated neutrophils in vitro via classical complement pathway-dependent manner.

Publisher: Academic Press Country of Publication: England NLM ID: 8812164 Publication Model: Print Cited Medium: Print ISSN: 0896-8411 (Print) Linking ISSN: 08968411 NLM ISO Abbreviation: J Autoimmun Subsets: MEDLINE

Publication: London : Academic Press
Original Publication: London ; San Diego : Academic Press, c1988-

Antibodies, Antineutrophil Cytoplasmic/*immunology ; Complement Pathway, Classical/*immunology ; Interleukin-17/*metabolism ; Neutrophil Activation/*immunology ; Neutrophils/*immunology; Animals ; Antibodies, Antineutrophil Cytoplasmic/blood ; Antibodies, Antineutrophil Cytoplasmic/pharmacology ; Autoantibodies/immunology ; Cells, Cultured ; Complement Pathway, Classical/drug effects ; Male ; Membrane Glycoproteins/immunology ; Mice ; Mice, Inbred C57BL ; Neutrophil Activation/drug effects ; Neutrophils/drug effects ; Peroxidase/immunology ; Vasculitis/immunology ; Vasculitis/metabolism

The elevation of serum anti-neutrophil cytoplasmic autoantibodies (ANCA) is significantly associated with the progression of some patients with systemic vasculitis. Especially, myeloperoxidase-specific ANCA (MPO-ANCA) play a pivotal role in the progression of systemic vasculitis including crescentic glomerulonephritis. Here we demonstrated that MPO-ANCA-activated neutrophils allow the local environment to differentiate Th(17) cells through IL-6, IL-17A, and IL-23 production. We found a variety of elevated serum cytokines, especially IL-17A, in ANCA-mediated systemic vasculitis mice. Furthermore, activated peritoneal neutrophils in vitro also produced IL-17A and IL-23 in response to MPO-ANCA. Co-stimulation of fungal mannoprotein and complements significantly enhanced the MPO-ANCA-mediated IL-17A expression, but F(ab)'(2) fragments of MPO-ANCA diminished the cytokine response. These results suggest that the activated neutrophils produce IL-17A and IL-23 in response to MPO-ANCA via their Fc-region and classical complement pathway, which initiate the first steps of chronic autoimmune inflammation by allowing the local environment to develop Th(17)-mediated autoimmunity.

0 (Antibodies, Antineutrophil Cytoplasmic)
0 (Autoantibodies)
0 (Interleukin-17)
0 (Membrane Glycoproteins)
0 (mannoproteins)
EC 1.11.1.7 (Peroxidase)

Date Created: 20080527 Date Completed: 20090129 Latest Revision: 20181201

20250114

10.1016/j.jaut.2008.03.006

18501296