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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2002-10-14
pubmed:abstractText
Stimulation of monocytes (MO) through receptors for the Fc region of immunoglobulin G (FcgammaR) 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 FcgammaR in high density produces high levels of tumor necrosis factor alpha (TNF-alpha) compared with FcgammaR-negative MO. Here, we show that cross-linking MO via FcgammaRI or FcgammaRII but not via FcgammaRIII activates nuclear regulatory factor-kappaB (NF-kappaB), a transcription factor involved in regulation of TNF-alpha. NF-kappaB activation peaked at 2.75 h after FcgammaRI cross-linking, involved p65 and p50 (heterodimer) and not c-rel-containing NF-kappaB complexes, and was mediated via IkappaB degradation. Cross-linking FcgammaRI, -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 FcgammaR cross-linking was not mediated by TNF-alpha, as the presence of an anti-TNF-alpha Ab could not restore the reduced IL-12 production. Decreased IL-12 production correlated with reduced antigen presentation capacity (P<0.01) in the FcgammaR-cross-linked MO. Blood MO can give rise to myeloid dendritic cells (DC). FcgammaR 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 FcgammaRI cross-linked DC. These results suggest that signals mediated via FcgammaRI, -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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0741-5400
pubmed:author
pubmed:issnType
Print
pubmed:volume
72
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
657-67
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
FcgammaR cross-linking mediates NF-kappaB activation, reduced antigen presentation capacity, and decreased IL-12 production in monocytes without modulation of myeloid dendritic cell development.
pubmed:affiliation
Department of Medicine, University of Massachusetts Medical Center, Worcester, MA 01605, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.