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

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.

• Authors: 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
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 202 Issue 6 Pg. 1807-1814 (03 15 2019) ISSN: 1550-6606 [Electronic] United States
• PMID: 30718300 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 by The American Association of Immunologists, Inc.

Chemical References

• Interleukin-1beta
• Serum Amyloid P-Component
• PTX3 protein
• Uric Acid
• C-Reactive Protein

Topics

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