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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

The Long Pentraxin 3 Contributes to Joint Inflammation in Gout by Facilitating the Phagocytosis of Monosodium Urate Crystals

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Autor(es):
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Batista, V, Nathalia ; Barbagallo, Marialuisa [1] ; Oliveira, Vivian L. S. [2] ; Castro-Gomes, Thiago [3] ; Oliveira, Rene D. R. [4] ; Louzada-Junior, Paulo [4] ; Pinheiro, Geraldo R. C. [5] ; Mantovani, Alberto [6, 7] ; Teixeira, Mauro M. [2] ; Garlanda, Cecilia [1, 6] ; Amaral, Flavio A. [2]
Número total de Autores: 11
Afiliação do(s) autor(es):
[1] Humanitas Res Hosp, I-20089 Rozzano - Italy
[2] Batista, Nathalia, V, Univ Fed Minas Gerais, Inst Biol Sci, Dept Biochem & Immunol, Lab Immunopharmacol, BR-31270901 Belo Horizonte, MG - Brazil
[3] Univ Fed Minas Gerais, Inst Biol Sci, Dept Parasitol, BR-31270901 Belo Horizonte, MG - Brazil
[4] Univ Sao Paulo, Ribeirao Preto Med Sch, Div Rheumatol, BR-1409900 Sao Paulo - Brazil
[5] Univ Estado Rio De Janeiro, Discipline Rheumatol, BR-20550900 Rio De Janeiro - Brazil
[6] Humanitas Univ, Via Levi Montalcini, I-20090 Pieve Emanuele - Italy
[7] Queen Mary Univ London, William Harvey Res Inst, London EC1M 6BQ - England
Número total de Afiliações: 7
Tipo de documento: Artigo Científico
Fonte: JOURNAL OF IMMUNOLOGY; v. 202, n. 6, p. 1807-1814, MAR 15 2019.
Citações Web of Science: 0
Resumo

The purpose of this study was to investigate the role of pentraxin 3 (PTX3), a pivotal component of the innate immune system, in gout. Levels of PTX3 and IL-1 beta in human samples were evaluated by ELISA. Development of murine gout was evaluated through the levels of cytokines (PTX3, CXCL1, and IL-1 beta) and neutrophil recruitment into the joint cavity. Phagocytosis of monosodium urate (MSU) crystals and caspase-1 activation were determined by flow cytometer. Acute gout patients showed elevated concentration of PTX3 in plasma and synovial fluid as compared with healthy and osteoarthritic subjects. Moreover, there was a positive correlation between intra-articular PTX3 and IL-1 beta levels. PTX3 was induced in the periarticular tissue of mice postinjection of MSU crystals. Importantly, Ptx3-deficient mice showed reduced inflammation in response to MSU crystal injection compared with wild-type mice, including reduction of neutrophil recruitment into the joint cavity and IL-1 beta and CXCL1 production. Interestingly, addition of PTX3 in vitro enhanced MSU crystal phagocytosis by monocytes and resulted in higher production of IL-1 beta by macrophages. This contribution of PTX3 to the phagocytosis of MSU crystals and consequent production of IL-1 beta occurred through a mechanism mainly dependent on Fc gamma RIII. Thus, our results suggest that PTX3 acts as a humoral pattern recognition molecule in gout facilitating MSU crystal phagocytosis and contributing to the pathogenesis of gouty arthritis. (AU)

Processo FAPESP: 13/08216-2 - CPDI - Centro de Pesquisa em Doenças Inflamatórias
Beneficiário:Fernando de Queiroz Cunha
Linha de fomento: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs