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

Nathália V Batista, Marialuisa Barbagallo, Vivian L S Oliveira, Thiago Castro-Gomes, Rene D R Oliveira, Paulo Louzada-Junior, Geraldo R C Pinheiro, Alberto Mantovani, Mauro M Teixeira, Cecilia Garlanda, Flávio A Amaral

Research output: Contribution to journalArticle

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-1β in human samples were evaluated by ELISA. Development of murine gout was evaluated through the levels of cytokines (PTX3, CXCL1, and IL-1β) 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-1β 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-1β and CXCL1 production. Interestingly, addition of PTX3 in vitro enhanced MSU crystal phagocytosis by monocytes and resulted in higher production of IL-1β by macrophages. This contribution of PTX3 to the phagocytosis of MSU crystals and consequent production of IL-1β occurred through a mechanism mainly dependent on FcγRIII. 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.

Original languageEnglish
Pages (from-to)1807-1814
Number of pages8
JournalJournal of immunology (Baltimore, Md. : 1950)
Volume202
Issue number6
DOIs
Publication statusPublished - Mar 15 2019

Keywords

  • Animals
  • Arthritis, Gouty/immunology
  • C-Reactive Protein/immunology
  • Humans
  • Interleukin-1beta/immunology
  • Mice
  • Mice, Inbred C57BL
  • Phagocytosis/immunology
  • Serum Amyloid P-Component/immunology
  • Uric Acid/immunology

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    Batista, N. V., Barbagallo, M., Oliveira, V. L. S., Castro-Gomes, T., Oliveira, R. D. R., Louzada-Junior, P., Pinheiro, G. R. C., Mantovani, A., Teixeira, M. M., Garlanda, C., & Amaral, F. A. (2019). The Long Pentraxin 3 Contributes to Joint Inflammation in Gout by Facilitating the Phagocytosis of Monosodium Urate Crystals. Journal of immunology (Baltimore, Md. : 1950), 202(6), 1807-1814. https://doi.org/10.4049/jimmunol.1701531