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J Leukoc Biol. 2003 Jul;74(1):3-15.

Neutrophil-activating potential of antineutrophil cytoplasm autoantibodies.

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  • 1Department of Internal Medicine, University Hospital Groningen, The Netherlands.

Abstract

Accumulating in vivo and in vitro evidence supports the hypothesis that antineutrophil cytoplasm autoantibodies (ANCA) with specificity for proteinase 3 (PR3) and myeloperoxidase (MPO) are involved in the pathophysiology of small-vessel vasculitis. The best-described effector function of these autoantibodies is stimulation of neutrophils to produce reactive oxygen species and to release proteolytic enzymes. Neutrophil activation requires interaction of monomeric ANCA with PR3/MPO and Fcgamma receptors, but also other mechanisms--for instance, stimulation by ANCA-containing immune complexes--cannot be excluded. This review focuses on the mechanisms of neutrophil activation by ANCA. We discuss the molecules involved in ANCA binding to the neutrophil surface and in triggering the functional responses. We summarize current knowledge on the signal-transduction pathways initiated by ANCA and on the factors determining susceptibility of neutrophils to activation by these autoantibodies.

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PMID:
12832437
[PubMed - indexed for MEDLINE]
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