Octacalcium phosphate crystals induce inflammation in vivo through interleukin-1 but independent of the NLRP3 inflammasome in mice.
Arthritis Rheum
; 63(2): 422-33, 2011 Feb.
Article
em En
| MEDLINE
| ID: mdl-21279999
ABSTRACT
OBJECTIVE:
To determine the mechanisms involved in inflammatory responses to octacalcium phosphate (OCP) crystals in vivo.METHODS:
OCP crystal-induced inflammation was monitored using a peritoneal model of inflammation in mice with different deficiencies affecting interleukin-1 (IL-1) secretion (IL-1α(-/-) , IL-1ß(-/-) , ASC(-/-) , and NLRP3(-/-) mice) or in mice pretreated with IL-1 inhibitors (anakinra [recombinant IL-1 receptor antagonist] and anti-IL-1ß). The production of IL-1α, IL-1ß, and myeloid-related protein 8 (MRP-8)-MRP-14 complex was determined by enzyme-linked immunosorbent assay. Peritoneal neutrophil recruitment and cell viability were determined by flow cytometry. Depletion of mast cells or resident macrophages was performed by pretreatment with compound 48/80 or clodronate liposomes, respectively.RESULTS:
OCP crystals induced peritoneal inflammation, as demonstrated by neutrophil recruitment and up-modulation of IL-1α, IL-1ß, and MRP-8-MRP-14 complex, to levels comparable with those induced by monosodium urate monohydrate crystals. This OCP crystal-induced inflammation was both IL-1α- and IL-1ß-dependent, as shown by the inhibitory effects of anakinra and anti-IL-1ß antibody treatment. Accordingly, OCP crystal stimulation resulted in milder inflammation in IL-1α(-/-) and IL-1ß(-/-) mice. Interestingly, ASC(-/-) and NLRP3(-/-) mice did not show any alteration in their inflammation status in response to OCP crystals. Depletion of the resident macrophage population resulted in a significant decrease in crystal-induced neutrophil infiltration and proinflammatory cytokine production in vivo, whereas mast cell depletion had no effect. Finally, OCP crystals induced apoptosis/necrosis of peritoneal cells in vivo.CONCLUSION:
These data indicate that macrophages, rather than mast cells, are important for initiating and driving OCP crystal-induced inflammation. Additionally, OCP crystals induce IL-1-dependent peritoneal inflammation without requiring the NLRP3 inflammasome.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peritonite
/
Fosfatos de Cálcio
/
Proteínas de Transporte
/
Interleucina-1
/
Substitutos Ósseos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article