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

Citation
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
Citations number
37
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Urology & Nephrology","da verificare
Journal title
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
ISSN journal
1046-6673 → ACNP
Volume
11
Issue
9
Year of publication
2000
Pages
1639 - 1646
Database
ISI
SICI code
1046-6673(200009)11:9<1639:UOCACO>2.0.ZU;2-Y
Abstract
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.