title: The NLRP3 inflammasome is released as a particulate danger signal that amplifies the inflammatory response.
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.
authors: 1] Inflammation and Experimental Surgery Unit, CIBERehd, Institute for Bio-Health Research of Murcia, Clinical University Hospital Virgen de la Arrixaca, Murcia, Spain. [2].
authors: Alberto
authors: A
authors: Baroja-Mazo
authors: 1] Inflammation and Experimental Surgery Unit, CIBERehd, Institute for Bio-Health Research of Murcia, Clinical University Hospital Virgen de la Arrixaca, Murcia, Spain. [2].
authors: Fatima
authors: F
authors: Martín-Sánchez
authors: Inflammation and Experimental Surgery Unit, CIBERehd, Institute for Bio-Health Research of Murcia, Clinical University Hospital Virgen de la Arrixaca, Murcia, Spain.
authors: Ana I
authors: AI
authors: Gomez
authors: Inflammation and Experimental Surgery Unit, CIBERehd, Institute for Bio-Health Research of Murcia, Clinical University Hospital Virgen de la Arrixaca, Murcia, Spain.
authors: Carlos M
authors: CM
authors: Martínez
authors: Inflammation and Experimental Surgery Unit, CIBERehd, Institute for Bio-Health Research of Murcia, Clinical University Hospital Virgen de la Arrixaca, Murcia, Spain.
authors: Joaquín
authors: J
authors: Amores-Iniesta
authors: 1] Faculty of Life Sciences, University of Manchester, Manchester, UK. [2].
authors: Vincent
authors: V
authors: Compan
authors: Inflammation and Experimental Surgery Unit, CIBERehd, Institute for Bio-Health Research of Murcia, Clinical University Hospital Virgen de la Arrixaca, Murcia, Spain.
authors: Maria
authors: M
authors: Barberà-Cremades
authors: Department of Immunology-CDB, Hospital Clinic, Barcelona, Spain.
authors: Jordi
authors: J
authors: Yagüe
authors: Department of Immunology-CDB, Hospital Clinic, Barcelona, Spain.
authors: Estibaliz
authors: E
authors: Ruiz-Ortiz
authors: Reumathology Pediatric Unit, Hospital Sant Joan de Deu, Barcelona, Spain.
authors: Jordi
authors: J
authors: Antón
authors: Department of Internal Medicine, Hospital Vall d'Hebron, Barcelona, Spain.
authors: Segundo
authors: S
authors: Buján
authors: Experimental and Molecular Immunology and Neurogenetics, CNRS UMR 7355, University of Orleans, Orleans, France.
authors: Isabelle
authors: I
authors: Couillin
authors: Faculty of Life Sciences, University of Manchester, Manchester, UK.
authors: David
authors: D
authors: Brough
authors: Department of Immunology-CDB, Hospital Clinic, Barcelona, Spain.
authors: Juan I
authors: JI
authors: Arostegui
authors: 1] 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.
authors: Pablo
authors: 0000000296881804
authors: P
authors: Pelegrín
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins; D053468:CARD Signaling Adaptor Proteins; D002352:Carrier Proteins / Q000097:blood / Q000235:genetics / Q000276:immunology*; D020170:Caspase 1 / Q000235:genetics / Q000276:immunology*; D020169:Caspases / Q000235:genetics / Q000276:immunology; D053471:Caspases, Initiator; D002478:Cells, Cultured; D056587:Cryopyrin-Associated Periodic Syndromes / Q000097:blood; D003598:Cytoskeletal Proteins / Q000097:blood / Q000235:genetics / Q000276:immunology; D057809:HEK293 Cells; D006801:Humans; D058847:Inflammasomes / Q000097:blood / Q000276:immunology*; D007249:Inflammation / Q000276:immunology*; D053583:Interleukin-1beta / Q000097:blood / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D010587:Phagocytosis / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology
chemical_list: D051017:Apoptosis Regulatory Proteins; D053468:CARD Signaling Adaptor Proteins; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D058847:Inflammasomes; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; C492716:Nlrp3 protein, mouse; C498534:Pycard protein, mouse; C101136:Casp4 protein, mouse; D020169:Caspases; D053471:Caspases, Initiator; D020170:Caspase 1