Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Blood. 2010 Sep 2;116(9):1570-3. doi: 10.1182/blood-2010-01-264218. Epub 2010 May 21.

Inflammasome activation in NADPH oxidase defective mononuclear phagocytes from patients with chronic granulomatous disease.

Author information

  • 1Department of Cellular Microbiology, Max Planck Institute for Infection Biology, Berlin, Germany.

Abstract

Chronic granulomatous disease (CGD) is an inherited disorder characterized by recurrent infections and deregulated inflammatory responses. CGD is caused by mutations in subunits of the NADPH oxidase, an enzyme that generates reactive oxygen species in phagocytes. To elucidate the contribution of the proinflammatory protease caspase-1 to aberrant inflammatory reactions in CGD, we analyzed cells isolated from patients with defects in the phagocyte oxidase subunits p22phox, p47phox or gp91phox. We report that mononuclear phagocytes from CGD patients activated caspase-1 and produced biologically active interleukin-1beta (IL-1beta) in response to danger signals. Notably, caspase-1 activation and IL-1beta secretion from CGD monocytes was elevated in asymptomatic patients and strongly increased in patients with noninfectious inflammatory conditions. Treatment with IL-1 receptor antagonist reduced IL-1 production in monocytes ex vivo and during medical therapy. Our results identify phagocyte oxidase defective monocytes as a source of elevated IL-1 and provide a potential therapeutic option to ameliorate inflammatory conditions associated with CGD.

Comment in

PMID:
20495074
[PubMed - indexed for MEDLINE]
PMCID:
PMC2938844
Free PMC Article

Images from this publication.See all images (2)Free text

Figure 1
Figure 2
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

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