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

Yvonne Drechsler, Sangeeta Chavan, Donna Catalano, Pranoti Mandrekar, Gyongyi Szabo

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Stimulation of monocytes (MO) through receptors for the Fc region of immunoglobulin G (FcγR) 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 FcγR in high density produces high levels of tumor necrosis factor α (TNF-α) compared with FcγR-negative MO. Here, we show that cross-linking MO via FcγRI or FcγRII but not via FcγRIII activates nuclear regulatory factor-κB (NF-κB), a transcription factor involved in regulation of TNF-α. NF-κB activation peaked at 2.75 h after FcγRI cross-linking, involved p65 and p50 (heterodimer) and not c-rel-containing NF-κB complexes, and was mediated via IκB degradation. Cross-linking FcγRI, -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 FcγR cross-linking was not mediated by TNF-α, as the presence of an anti-TNF-α Ab could not restore the reduced IL-12 production. Decreased IL-12 production correlated with reduced antigen presentation capacity (P<0.01) in the FcγR-cross-linked MO. Blood MO can give rise to myeloid dendritic cells (DC). FcγR 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 (CD1a, CD80, CD86) was not different between control and FcγRI cross-linked DC. These results suggest that signals mediated via FcγRI, -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.

Original languageEnglish
Pages (from-to)657-667
Number of pages11
JournalJournal of Leukocyte Biology
Volume72
Issue number4
Publication statusPublished - Oct 1 2002

Keywords

  • FcγRI (CD64)
  • FcγRIII (C16)
  • FcγRIII (C32)
  • TNF-α

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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