期刊
JOURNAL OF IMMUNOLOGY
卷 202, 期 6, 页码 1807-1814出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1701531
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资金
- Brazilian National Council for Scientific and Technological Development
- National Institute of Science and Technology in Dengue and Host-Parasite Interactions [465425/2014-3]
- Minas Gerais State Agency for Research and Development (FAPEMIG)
- Sao Paulo Research Foundation [2013/08216-2]
- University of Sao Paulo Nucleo de Pesquisa em Doencas Inflamatorias [11.1.21625.01.0]
- European Commission [ERC - 669415]
- Italian Association for Cancer Research (AIRC)
- Fondazione Cariplo [2015-0564]
- Italian Ministry of Health [RF-2013-02355470]
- Italian Ministry of Education, University and Research [PRIN 2015YYKPNN]
- Italian Association for Cancer Research (IG)
- Italian Association for Cancer Research (5x1000)
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.
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