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

Author(s):Show less -

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]

Affiliation

^[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

• Document type: Journal article
• Source: JOURNAL OF IMMUNOLOGY; v. 202, n. 6, p. 1807-1814, MAR 15 2019.
• Web of Science Citations: 0

Abstract

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)

• FAPESP's process: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases
• Grantee: Fernando de Queiroz Cunha
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC