R. Nowack et al., Upregulation of CD14 and CD18 on monocytes in vitro by antineutrophil cytoplasmic autoantibodies, J AM S NEPH, 11(9), 2000, pp. 1639-1646
The expression of CD14, CD18, and major histocompatibility complex II on un
primed monocytes from healthy donors after incubation with IgG from patient
s with antineutrophil cytoplasmic autoantibody (ANCA)-positive active Wegen
er's granulomatosis (n = 6) and microscopic polyangiitis (n = 6) in compari
son with IgG from healthy controls (n = 6) was studied. Monocytes were incu
bated with IgG (100 mu g/ml) at 37 degrees C, and expression of antigens wa
s measured by fluorescence-activated cell sorter after 18 h. Cytoplasmic AN
CA (C-ANCA) IgG and perinuclear ANCA (P-ANCA) IgG in comparison with contro
l IgG increased the expression of CD 14 (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 expres
sion. 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) fragment
s of C- and P-ANCA IgG also increased expression of CD14 and CD18 as compar
ed with control IgG F(ab)(2), but for CD14 less than with complete IgG. ANC
A IgG depleted of antiproteinase 3 and antimyeloperoxidase antibodies by im
munoadsorption failed to upregulate CD14. Monoclonal murine antibodies agai
nst proteinase 3 and myeloperoxidase yielded a strong upregulation of CD14
when compared with an isotype control or human control IgG. The data show t
hat CD14 and CD18 are upregulated on monocytes by C- and P-ANCA IgG in vitr
o, as well as by monoclonal antibodies against proteinase 3 and myeloperoxi
dase and that this effect is not dependent on Fc gamma receptor crosslinkin
g. Upregulation of CD14 and CD18 on monocytes by ANCA suggests a pathogenet
ic role of ANCA monocyte interactions in systemic vasculitis.