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

被引：635

作者：

Baroja-Mazo, Alberto ^{[1
]}

Martin-Sanchez, Fatima ^{[1
]}

Gomez, Ana I. ^{[1
]}

Martinez, Carlos M. ^{[1
]}

Amores-Iniesta, Joaquin ^{[1
]}

Compan, Vincent ^{[2
]}

Barbera-Cremades, Maria ^{[1
]}

Yaguee, Jordi ^{[3
]}

Ruiz-Ortiz, Estibaliz ^{[3
]}

Anton, Jordi ^{[4
]}

Bujan, Segundo ^{[5
]}

Couillin, Isabelle ^{[6
]}

Brough, David ^{[2
]}

Arostegui, Juan I. ^{[3
]}

Pelegrin, Pablo ^{[1
,2
]}

机构：

[1] Clin Univ Hosp Virgen de la Arrixaca, Inst Biohlth Res Murcia, CIBERehd, Inflammat & Expt Surg Unit, Murcia, Spain

[2] Univ Manchester, Fac Life Sci, Manchester, Lancs, England

[3] Hosp Clin Barcelona, Dept Immunol CDB, Barcelona, Spain

[4] Hosp St Joan de Deu, Reumathol Pediat Unit, Barcelona, Spain

[5] Hosp Valle De Hebron, Dept Internal Med, Barcelona, Spain

[6] Univ Orleans, CNRS UMR 7355, Orleans, France

来源：

NATURE IMMUNOLOGY | 2014年 / 15卷 / 08期

基金：

英国惠康基金;

关键词：

NALP3; INFLAMMASOME; ACTIVATION; CASPASE-1; ASC; IL-1-BETA; MECHANISM; PURIFICATION; EXPRESSION; SECRETION; AUTOPHAGY;

D O I：

10.1038/ni.2919

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Assembly of the NLRP3 inflammasome activates caspase-1 and mediates the processing and release of the leaderless cytokine IL-1 beta 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.

引用

页码：738 / +

页数：13

共 49 条

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