Format

Send to

Choose Destination
See comment in PubMed Commons below
J Exp Med. 1997 Jun 2;185(11):1987-95.

Regulation of interleukin-12 by complement receptor 3 signaling.

Author information

  • 1Mucosal Immunity Section, Laboratory of Clinical Investigation, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.

Abstract

Complement receptor type 3 (CR3, CD11b/CD18) serves as a receptor for a number of endogenous ligands and infectious organisms, and is involved in adhesion and host defense functions. Here, we report that signaling via CR3 plays an important role in regulating production of interleukin-12 (IL-12), a key mediator of cell-mediated immunity (CMI). We demonstrate with a variety of stimuli a dose-dependent, specific downregulation of IL-12 secretion by human monocytes in vitro after exposure to antibodies to CR3 (anti-CD11b and anti-CD18), as well as to the natural CR3 ligands, iC3b, and Histoplasma capsulatum. CR3 antibodies also suppressed interferon-gamma (IFN-gamma) production in cultures of human peripheral blood mononuclear cells (PBMC). We determined that one mechanism by which CR3 antibodies may suppress IL-12 production is by the inhibition of IFN-gamma-induced tyrosine phosphorylation. Finally, in a murine model of IL-12-dependent septic shock, we provide evidence that administration of CR3 antibodies leads to suppression of IL-12 and IFN-gamma in vivo. Our studies thus define a novel role for CR3 in regulating CMI functions via IL-12.

PMID:
9166428
PMCID:
PMC2196332
[PubMed - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk