{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T12:45:32Z","timestamp":1791117932451,"version":"4.1.0"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2007,5,29]],"date-time":"2007-05-29T00:00:00Z","timestamp":1180396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Arthritis Society and the National Institutes of Health","award":["5R01AR052614-03"],"award-info":[{"award-number":["5R01AR052614-03"]}]},{"DOI":"10.13039\/501100006538","name":"Canadian Arthritis Network","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006538","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The deposition of monosodium urate (MSU) crystals in the joints of humans leads to an extremely acute, inflammatory reaction, commonly known as gout, characterized by a massive infiltration of neutrophils. Direct interactions of MSU crystals with human neutrophils and inflammatory mediators are crucial to the induction and perpetuation of gout attacks. The intracellular signaling events initiated by the physical interaction between MSU crystals and neutrophils depend on the activation of specific tyrosine kinases (Src and Syk, in particular). In addition, PI-3Ks may be involved. The present study investigates the involvement of the PI-3K family in the mediation of the responses of human neutrophils to MSU crystals. The results obtained indicate that the interaction of MSU crystals with human neutrophils leads to the stimulation of class Ia PI-3Ks by a mechanism that is dependent on the tyrosine kinase Syk. We also found an increase in the amount of p85 associated with the Nonidet P-40-insoluble fraction derived from MSU crystal-stimulated human neutrophils. Furthermore, MSU crystals induce the formation of a complex containing p85 and Syk, which is mediated by the Src family kinases. Finally, evidence is also obtained indicating that the activation of PI-3Ks by MSU crystals is a critical element regulating phospholipase D activation and degranulation of human neutrophils. The latter response is likely to be involved in the joint and tissue damage that occurs in gouty patients.<\/jats:p>","DOI":"10.1189\/jlb.0307174","type":"journal-article","created":{"date-parts":[[2007,5,30]],"date-time":"2007-05-30T01:36:15Z","timestamp":1180488975000},"page":"763-773","source":"Crossref","is-referenced-by-count":44,"title":["Crystal-induced neutrophil activation. IX. Syk-dependent activation of class Ia phosphatidylinositol 3-kinase"],"prefix":"10.1093","volume":"82","author":[{"given":"Oana","family":"Popa-Nita","sequence":"first","affiliation":[{"name":"Centre de Recherche en Rhumatologie et Immunologie, Centre de Recherche du CHUQ, Department of Medicine, Faculty of Medicine, Laval University , Qu\u00e9bec , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuelle","family":"Rollet-Labelle","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Rhumatologie et Immunologie, Centre de Recherche du CHUQ, Department of Medicine, Faculty of Medicine, Laval University , Qu\u00e9bec , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Thibault","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Rhumatologie et Immunologie, Centre de Recherche du CHUQ, Department of Medicine, Faculty of Medicine, Laval University , Qu\u00e9bec , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Gilbert","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Rhumatologie et Immunologie, Centre de Recherche du CHUQ, Department of Medicine, Faculty of Medicine, Laval University , Qu\u00e9bec , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvain G","family":"Bourgoin","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Rhumatologie et Immunologie, Centre de Recherche du CHUQ, Department of Medicine, Faculty of Medicine, Laval University , Qu\u00e9bec , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul H","family":"Naccache","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Rhumatologie et Immunologie, Centre de Recherche du CHUQ, Department of Medicine, Faculty of Medicine, Laval University , Qu\u00e9bec , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2007,5,29]]},"reference":[{"key":"2023033006502071000_","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1007\/s11926-004-0073-5","article-title":"How crystals damage tissue","volume":"6","author":"Molloy","year":"2004","journal-title":"Curr. Rheumatol. Rep."},{"key":"2023033006502071000_","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S0046-8177(73)80013-9","article-title":"The synovitis of acute gouty arthritis. A light and electron microscopic study","volume":"4","author":"Agudelo","year":"1973","journal-title":"Hum. Pathol."},{"key":"2023033006502071000_","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1002\/art.1780050610","article-title":"The old and new concepts of acute gouty arthritis","volume":"5","author":"Seegmiller","year":"1962","journal-title":"Arthritis Rheum."},{"key":"2023033006502071000_","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1002\/art.1780120305","article-title":"Polymorphonuclear leukocyte motility in vitro. II. Stimulatory effect of monosodium urate crystals and urate in solution; partial inhibition by colchicine and indomethacin","volume":"12","author":"Phelps","year":"1969","journal-title":"Arthritis Rheum."},{"key":"2023033006502071000_","first-page":"559","article-title":"Analysis of the cytokine network among tumor necrosis factor \u03b1, interleukin-1\u03b2, interleukin-8, and interleukin-1 receptor antagonist in monosodium urate crystal-induced rabbit arthritis","volume":"78","author":"Matsukawa","year":"1998","journal-title":"Lab. 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Exp. Med."},{"key":"2023033006502071000_","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/0076-6879(88)62076-3","article-title":"Crystal-induced chemotactic factor","volume":"162","author":"Spilberg","year":"1988","journal-title":"Methods Enzymol."},{"key":"2023033006502071000_","first-page":"928","article-title":"Characterization of an activation factor released from human neutrophils after stimulation by triclinic monosodium urate crystals","volume":"33","author":"Desaulniers","year":"2006","journal-title":"J. Rheumatol."},{"key":"2023033006502071000_","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1172\/JCI116759","article-title":"Crystal-induced neutrophil activation. IV. Specific inhibition of tyrosine phosphorylation by colchicine","volume":"92","author":"Roberge","year":"1993","journal-title":"J. Clin. 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Immunol."},{"key":"2023033006502071000_","doi-asserted-by":"crossref","first-page":"5795","DOI":"10.1073\/pnas.0631579100","article-title":"Resistance of cell membranes to different detergents","volume":"100","author":"Schuck","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023033006502071000_","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.it.2005.02.002","article-title":"Src and Syk kinases: key regulators of phagocytic cell activation","volume":"26","author":"Berton","year":"2005","journal-title":"Trends Immunol."},{"key":"2023033006502071000_","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1074\/jbc.271.2.695","article-title":"Discovery of a novel, potent, and Src family-selective tyrosine kinase inhibitor. Study of Lck- and FynT-dependent T cell activation","volume":"271","author":"Hanke","year":"1996","journal-title":"J. Biol. Chem."},{"key":"2023033006502071000_","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1002\/art.1780360119","article-title":"Crystal-induced neutrophil activation. II. Evidence for the activation of a phosphatidylcholine-specific phospholipase D","volume":"36","author":"Naccache","year":"1993","journal-title":"Arthritis Rheum."},{"key":"2023033006502071000_","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/0006-2952(93)90358-4","article-title":"Association between leukotriene B4-induced phospholipase D activation and degranulation of human neutrophils","volume":"46","author":"Zhou","year":"1993","journal-title":"Biochem. Pharmacol."},{"key":"2023033006502071000_","first-page":"159","article-title":"Lysozyme in human neutrophils and plasma. 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Involvment of Fc\u03b3RIIIB (CD16) and CD11b in response to inflammatory microcrystals","volume":"12","author":"Barabe","year":"1998","journal-title":"FASEB J."},{"key":"2023033006502071000_","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1042\/BJ20050129","article-title":"CD16b associates with high-density, detergent-resistant membranes in human neutrophils","volume":"393","author":"Fernandes","year":"2006","journal-title":"Biochem. J."},{"key":"2023033006502071000_","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1189\/jlb.0106019","article-title":"Differential kinase requirements in human and mouse Fc-\u03b3 receptor phagocytosis and endocytosis","volume":"80","author":"Huang","year":"2006","journal-title":"J. Leukoc. 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