{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T04:38:21Z","timestamp":1773290301605,"version":"3.50.1"},"reference-count":40,"publisher":"American Society of Hematology","issue":"5","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2001,9,1]]},"abstract":"<jats:p>In systemic vasculitis, interactions between antineutrophil cytoplasm autoantibodies (ANCAs) and neutrophils initiate endothelial and vascular injury. ANCAs directed against either myeloperoxidase (MPO) or proteinase 3 (PR3) can activate cytokine-primed neutrophils by binding cell surface\u2013expressed MPO or PR3, with the concurrent engagement of Fc\u03b3 receptors (Fc\u03b3R). Because roles for phospholipase D (PLD) and phosphatidylinositol 3 kinase (PI3K) have been demonstrated in Fc\u03b3R activation of neutrophils, this study investigated the hypothesis that ANCA stimulation of neutrophils involved a similar engagement of Fc\u03b3R and activation of PLD and PI3K. Pretreatment of tumor necrosis factor (TNF) \u03b1-primed neutrophils with antibodies against Fc\u03b3RII and Fc\u03b3RIII inhibited MPO-ANCA and PR3-ANCA induced superoxide generation, confirming that Fc\u03b3R ligation is involved in ANCA-mediated neutrophil activation. However, although stimulation of TNF-\u03b1\u2013primed neutrophils by conventional Fc\u03b3R ligation, either using antibody-mediated cross-linking of Fc\u03b3R or aggregated IgG, induced PLD activation, ANCA stimulation did not. Moreover, although ANCA-induced neutrophil activation results in significant PI3K activation\u2014as assessed by phosphatidylinositol 3,4,5-triphosphate generation\u2014conventional Fc\u03b3R ligation, but not ANCA, activates the p85\/p110 PI3K subtype. Inhibition of ANCA-induced superoxide generation with pertussis toxin suggests that ANCAs activate the p101\/p110\u03b3 PI3K isoform. In addition, the kinetics of activation of protein kinase B differs between conventional Fc\u03b3R ligation and ANCA stimulation of neutrophils. These results demonstrate that though ligation of Fc\u03b3RIIa and Fc\u03b3RIIIb may be necessary, it is likely that ANCAs require other membrane cofactors for neutrophil activation.<\/jats:p>","DOI":"10.1182\/blood.v98.5.1448","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T12:46:47Z","timestamp":1027774007000},"page":"1448-1455","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":84,"title":["Antineutrophil cytoplasm autoantibodies from patients with systemic vasculitis activate neutrophils through distinct signaling cascades: comparison with conventional Fc\u03b3 receptor ligation"],"prefix":"10.1182","volume":"98","author":[{"given":"Anne","family":"Ben-Smith","sequence":"first","affiliation":[{"name":"From the Renal Immunobiology, MRC Centre for Immune Regulation, the Department of Biochemistry, and the Institute for Cancer Studies, The Medical School, University of Birmingham, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen K.","family":"Dove","sequence":"additional","affiliation":[{"name":"From the Renal Immunobiology, MRC Centre for Immune Regulation, the Department of Biochemistry, and the Institute for Cancer Studies, The Medical School, University of Birmingham, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashley","family":"Martin","sequence":"additional","affiliation":[{"name":"From the Renal Immunobiology, MRC Centre for Immune Regulation, the Department of Biochemistry, and the Institute for Cancer Studies, The Medical School, University of Birmingham, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael J. 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