Format

Send to:

Choose Destination
See comment in PubMed Commons below
Nat Immunol. 2014 Aug;15(8):738-48. doi: 10.1038/ni.2919. Epub 2014 Jun 22.

The NLRP3 inflammasome is released as a particulate danger signal that amplifies the inflammatory response.

Author information

  • 11] Inflammation and Experimental Surgery Unit, CIBERehd, Institute for Bio-Health Research of Murcia, Clinical University Hospital Virgen de la Arrixaca, Murcia, Spain. [2].
  • 2Inflammation and Experimental Surgery Unit, CIBERehd, Institute for Bio-Health Research of Murcia, Clinical University Hospital Virgen de la Arrixaca, Murcia, Spain.
  • 31] Faculty of Life Sciences, University of Manchester, Manchester, UK. [2].
  • 4Department of Immunology-CDB, Hospital Clinic, Barcelona, Spain.
  • 5Reumathology Pediatric Unit, Hospital Sant Joan de Deu, Barcelona, Spain.
  • 6Department of Internal Medicine, Hospital Vall d'Hebron, Barcelona, Spain.
  • 7Experimental and Molecular Immunology and Neurogenetics, CNRS UMR 7355, University of Orleans, Orleans, France.
  • 8Faculty of Life Sciences, University of Manchester, Manchester, UK.
  • 91] Inflammation and Experimental Surgery Unit, CIBERehd, Institute for Bio-Health Research of Murcia, Clinical University Hospital Virgen de la Arrixaca, Murcia, Spain. [2] Faculty of Life Sciences, University of Manchester, Manchester, UK.

Abstract

Assembly of the NLRP3 inflammasome activates caspase-1 and mediates the processing and release of the leaderless cytokine IL-1β and thereby serves a central role in the inflammatory response and in diverse human diseases. Here we found that upon activation of caspase-1, oligomeric NLRP3 inflammasome particles were released from macrophages. Recombinant oligomeric protein particles composed of the adaptor ASC or the p.D303N mutant form of NLRP3 associated with cryopyrin-associated periodic syndromes (CAPS) stimulated further activation of caspase-1 extracellularly, as well as intracellularly after phagocytosis by surrounding macrophages. We found oligomeric ASC particles in the serum of patients with active CAPS but not in that of patients with other inherited autoinflammatory diseases. Our findings support a model whereby the NLRP3 inflammasome, acting as an extracellular oligomeric complex, amplifies the inflammatory response.

PMID:
24952504
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group
    Loading ...
    Write to the Help Desk