Upregulation of CD14 and CD18 on monocytes In vitro by antineutrophil cytoplasmic autoantibodies.

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.