title: Upregulation of CD14 and CD18 on monocytes In vitro by antineutrophil cytoplasmic autoantibodies.
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 microg/ml) at 37 degrees 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.
authors.affiliation: Vth Medical Clinic (Nephrology, Endocrinology), University-Clinic Mannheim, Medical Faculty of the University of Heidelberg, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Nowack
authors.affiliation: Vth Medical Clinic (Nephrology, Endocrinology), University-Clinic Mannheim, Medical Faculty of the University of Heidelberg, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Schwalbe
authors.affiliation: Vth Medical Clinic (Nephrology, Endocrinology), University-Clinic Mannheim, Medical Faculty of the University of Heidelberg, Germany.
authors.forename: Luis-Felipe
authors.initials: LF
authors.lastname: Flores-Suárez
authors.affiliation: Vth Medical Clinic (Nephrology, Endocrinology), University-Clinic Mannheim, Medical Faculty of the University of Heidelberg, Germany.
authors.forename: Benito
authors.initials: B
authors.lastname: Yard
authors.affiliation: Vth Medical Clinic (Nephrology, Endocrinology), University-Clinic Mannheim, Medical Faculty of the University of Heidelberg, Germany.
authors.forename: Fokko J
authors.initials: FJ
authors.lastname: VAN DER Woude
mesh_terms: D000906:Antibodies / Q000302:isolation & purification; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000941:Antigens / Q000378:metabolism; D018821:CD18 Antigens / Q000378:metabolism*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D007074:Immunoglobulin G / Q000494:pharmacology; D018950:Lipopolysaccharide Receptors / Q000235:genetics / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism*; D053146:Myeloblastin; D009195:Peroxidase / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D012697:Serine Endopeptidases / Q000276:immunology; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D000906:Antibodies; D019268:Antibodies, Antineutrophil Cytoplasmic; D000911:Antibodies, Monoclonal; D000941:Antigens; D018821:CD18 Antigens; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D018950:Lipopolysaccharide Receptors; D012333:RNA, Messenger; D009195:Peroxidase; D012697:Serine Endopeptidases; D053146:Myeloblastin