{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T17:43:44Z","timestamp":1790185424788,"version":"4.1.0"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2017,5,26]],"date-time":"2017-05-26T00:00:00Z","timestamp":1495756800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,5,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Gout is one of the most painful types of arthritis that arises when the body mounts an acute inflammatory reaction against a crystallized form of uric acid known as monosodium urate crystals (MSUs). Although MSUs are known to activate neutrophils, the most abundant leukocyte in the synovial fluid of patients with gout, few studies have investigated the effect on neutrophils of the simultaneous stimulation with MSU and proinflammatory mediators in the inflamed joint. Herein, we focused on a protein that is highly expressed in the synovium in gout, S100A9. The predominant expression of S100A9 in and around blood vessels suggests it may prime neutrophils during their migration toward the inflamed joint. Using a combination of functional and signaling assays, we found that S100A9 enhances the production of radical oxygen species as well as IL-1 and IL-8 release by human neutrophils activated with MSU. Moreover, upstream and downstream signaling events activated by MSUs in human neutrophils were also potentiated by S100A9, including the mobilization of intracellular calcium stores, tyrosine phosphorylation, the serine phosphorylation of PKC substrates, Akt, and p38. We also show that S100A9 alone increases glycolysis in human neutrophils, which is suggestive of an additional mechanism through which neutrophils can be primed. Together, our observations indicate a novel way in which S100A9 may contribute to the pathogenesis of gout, by priming neutrophils to respond to MSUs.<\/jats:p>","DOI":"10.1189\/jlb.3ma0117-020r","type":"journal-article","created":{"date-parts":[[2017,5,27]],"date-time":"2017-05-27T00:50:19Z","timestamp":1495846219000},"page":"805-813","source":"Crossref","is-referenced-by-count":17,"title":["S100A9 potentiates the activation of neutrophils by the etiological agent of gout, monosodium urate crystals"],"prefix":"10.1093","volume":"102","author":[{"given":"Louis-Simon","family":"Rousseau","sequence":"first","affiliation":[{"name":"Department of Microbiology-Infectious Diseases and Immunology, Faculty of Medicine, Laval University , Ville de Qu\u00e9bec, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Par\u00e9","sequence":"additional","affiliation":[{"name":"Department of Microbiology-Infectious Diseases and Immunology, Faculty of Medicine, Laval University , Ville de Qu\u00e9bec, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asmaa","family":"Lachhab","sequence":"additional","affiliation":[{"name":"Department of Microbiology-Infectious Diseases and Immunology, Faculty of Medicine, Laval University , Ville de Qu\u00e9bec, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul H","family":"Naccache","sequence":"additional","affiliation":[{"name":"Department of Microbiology-Infectious Diseases and Immunology, Faculty of Medicine, Laval University , Ville de Qu\u00e9bec, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Marceau","sequence":"additional","affiliation":[{"name":"Department of Microbiology-Infectious Diseases and Immunology, Faculty of Medicine, Laval University , Ville de Qu\u00e9bec, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Tessier","sequence":"additional","affiliation":[{"name":"Department of Microbiology-Infectious Diseases and Immunology, Faculty of Medicine, Laval University , Ville de Qu\u00e9bec, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Pelletier","sequence":"additional","affiliation":[{"name":"Department of Microbiology-Infectious Diseases and Immunology, Faculty of Medicine, Laval University , Ville de Qu\u00e9bec, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Department of Microbiology-Infectious Diseases and Immunology, Faculty of Medicine, Laval University , Ville de Qu\u00e9bec, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,5,26]]},"reference":[{"key":"2023013012233480900_B1","doi-asserted-by":"crossref","first-page":"3136","DOI":"10.1002\/art.30520","article-title":"Prevalence of gout and hyperuricemia in the US general population: the National Health and Nutrition Examination Survey 2007-2008","volume":"63","author":"Zhu","year":"2011","journal-title":"Arthritis Rheum."},{"key":"2023013012233480900_B2","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1007\/s11926-013-0400-9","article-title":"The crystallization of monosodium urate","volume":"16","author":"Martillo","year":"2014","journal-title":"Curr. Rheumatol. Rep."},{"key":"2023013012233480900_B3","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1016\/j.clinthera.2014.07.017","article-title":"Mechanism of action of colchicine in the treatment of gout","volume":"36","author":"Dalbeth","year":"2014","journal-title":"Clin. Ther."},{"key":"2023013012233480900_B4","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1038\/icb.2009.98","article-title":"Crystal-induced neutrophil activation","volume":"88","author":"Popa-Nita","year":"2010","journal-title":"Immunol. Cell Biol."},{"key":"2023013012233480900_B5","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1002\/art.38369","article-title":"Myeloid-related proteins 8 and 14 contribute to monosodium urate monohydrate crystal-induced inflammation in gout","volume":"66","author":"Holzinger","year":"2014","journal-title":"Arthritis Rheumatol."},{"key":"2023013012233480900_B6","first-page":"d1356","article-title":"S100 proteins: structure, functions and pathology","volume":"7","author":"Heizmann","year":"2002","journal-title":"Front. Biosci."},{"key":"2023013012233480900_B7","doi-asserted-by":"crossref","first-page":"7706","DOI":"10.1016\/S0021-9258(20)89506-4","article-title":"Identification of p8,14 as a highly abundant heterodimeric calcium binding protein complex of myeloid cells","volume":"266","author":"Edgeworth","year":"1991","journal-title":"J. Biol. Chem."},{"key":"2023013012233480900_B8","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1002\/1529-0131(200003)43:3<628::AID-ANR20>3.0.CO;2-X","article-title":"Myeloid-related proteins 8 and 14 are specifically secreted during interaction of phagocytes and activated endothelium and are useful markers for monitoring disease activity in pauciarticular-onset juvenile rheumatoid arthritis","volume":"43","author":"Frosch","year":"2000","journal-title":"Arthritis Rheum."},{"key":"2023013012233480900_B9","doi-asserted-by":"crossref","first-page":"9496","DOI":"10.1074\/jbc.272.14.9496","article-title":"Myeloid-related protein (MRP) 8 and MRP14, calcium-binding proteins of the S100 family, are secreted by activated monocytes via a novel, tubulin-dependent pathway","volume":"272","author":"Rammes","year":"1997","journal-title":"J. Biol. Chem."},{"issue":"7","key":"2023013012233480900_B10","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1038\/ncprheum0531","article-title":"Mechanisms of disease: a \u2018DAMP\u2019 view of inflammatory arthritis","volume":"3","author":"Foell","year":"2007","journal-title":"Nat. Clin. Pract. Rheumatol."},{"key":"2023013012233480900_B11","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1165\/rcmb.2002-0286OC","article-title":"Myeloid related protein-8\/14 stimulates interleukin-8 production in airway epithelial cells","volume":"29","author":"Ahmad","year":"2003","journal-title":"Am. J. Respir. Cell Mol. 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Redox Signal."},{"key":"2023013012233480900_B33","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1002\/jlb.62.4.444","article-title":"Attenuation of monosodium urate crystal-induced arthritis in rabbits by a neutralizing antibody against interleukin-8","volume":"62","author":"Nishimura","year":"1997","journal-title":"J. Leukoc. 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