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J Am Soc Nephrol 11:1639-1646, 2000
© 2000 American Society of Nephrology

Upregulation of CD14 and CD18 on Monocytes In Vitro by Antineutrophil Cytoplasmic Autoantibodies

RAINER NOWACK, KATHARINA SCHWALBE, LUIS-FELIPE FLORES-SUÁREZ, BENITO YARD and FOKKO J. VAN DER WOUDE

Vth Medical Clinic (Nephrology, Endocrinology), University-Clinic Mannheim, Medical Faculty of the University of Heidelberg, Germany.

Correspondence to Dr. Rainer Nowack, Vth Medical Clinic (Nephrology, Endocrinology), University-Clinic Mannheim, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany. Phone: 49-8382-5577; Fax: 49-8382-24091; E-mail: rnowack{at}t-online.de

Abstract. The expression of CD14, CD18, and major histocompatibility complex II on unprimed monocytes from healthy donors after incubation with IgG from patients with antineutrophil cytoplasmic autoantibody (ANCA)-positive active Wegener's granulomatosis (n = 6) and microscopic polyangiitis (n = 6) in comparison with IgG from healthy controls (n = 6) was studied. Monocytes were incubated with IgG (100 µg/ml) at 37°C, and expression of antigens was measured by fluorescence-activated cell sorter after 18 h. Cytoplasmic ANCA (C-ANCA) IgG and perinuclear ANCA (P-ANCA) IgG in comparison with control IgG increased the expression of CD14 (49.2% [SD: 37, P < 0.001], and 55.8% [SD: 41, P < 0.05]) and CD18 (11.4% [SD: 18, P < 0.01] and 8% [SD: 26, P < 0.05]) but did not change the major histocompatibility complex II expression. Upregulation of CD14 started after 6 h and reached a peak after 10 to 14 h of incubation and was not inhibited by polymyxin B. F(ab)2 fragments of C- and P-ANCA IgG also increased expression of CD14 and CD18 as compared with control IgG F(ab)2, but for CD14 less than with complete IgG. ANCA IgG depleted of antiproteinase 3 and antimyeloperoxidase antibodies by immunoadsorption failed to upregulate CD14. Monoclonal murine antibodies against proteinase 3 and myeloperoxidase yielded a strong upregulation of CD14 when compared with an isotype control or human control IgG. The data show that CD14 and CD18 are upregulated on monocytes by C- and P-ANCA IgG in vitro, as well as by monoclonal antibodies against proteinase 3 and myeloperoxidase and that this effect is not dependent on Fc{gamma} receptor crosslinking. Upregulation of CD14 and CD18 on monocytes by ANCA suggests a pathogenetic role of ANCA monocyte interactions in systemic vasculitis.




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