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(Journal of Leukocyte Biology. 2002;72:657-667.)
© 2002 by Society for Leukocyte Biology

FcR cross-linking mediates NF-B activation, reduced antigen presentation capacity, and decreased IL-12 production in monocytes without modulation of myeloid dendritic cell development

Department of Medicine, University of Massachusetts Medical Center, Worcester, MA

Correspondence: Gyongyi Szabo, M.D., Ph.D., Associate Professor, Division of Gastroenterology, Department of Medicine, University of Massachusetts Medical School, NRB Floor 2, 364 Plantation Street, Worcester, MA 01605. E-mail: gyongyi.szabo{at}umassmed.edu

Stimulation of monocytes (MO) through receptors for the Fc region of immunoglobulin G (FcR) activates a variety of responses, including phagocytosis, antibody (Ab)-dependent cellular cytotoxicity, and production of cytokines. We previously reported that the MO subpopulation that expresses FcR in high density produces high levels of tumor necrosis factor (TNF-) compared with FcR-negative MO. Here, we show that cross-linking MO via FcRI or FcRII but not via FcRIII activates nuclear regulatory factor-B (NF-B), a transcription factor involved in regulation of TNF-. NF-B activation peaked at 2.75 h after FcRI cross-linking, involved p65 and p50 (heterodimer) and not c-rel-containing NF-B complexes, and was mediated via IB degradation. Cross-linking FcRI, -II, as well as -III inhibited interleukin (IL)-12 (p70) production in MO, whether stimulated with Staphylococcal enterotoxin B (P<0.02) or lipopolysaccharide (P<0.02). Inhibition of IL-12 by FcR cross-linking was not mediated by TNF-, as the presence of an anti-TNF- Ab could not restore the reduced IL-12 production. Decreased IL-12 production correlated with reduced antigen presentation capacity (P<0.01) in the FcR-cross-linked MO. Blood MO can give rise to myeloid dendritic cells (DC). FcR cross-linking did not modulate in vitro maturation of MO to fully functional myeloid DC. Allostimulatory capacity in mixed leukocyte reaction and DC marker expression (CDla, CD80, CD86) was not different between control and FcRI cross-linked DC. These results suggest that signals mediated via FcRI, -II, and -III have overlapping yet distinct effects on MO, which are likely to be involved in the fine-tuning of the immune responses to various stimuli.

Key Words: FcRI (CD64) • FcRII (C32) • FcRIII (C16) • TNF-

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