{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T10:55:07Z","timestamp":1793962507523,"version":"4.8.0"},"reference-count":23,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2008,12,30]],"date-time":"2008-12-30T00:00:00Z","timestamp":1230595200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2009,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To determine whether infiltrating monocytes, neutrophils, or resident macrophages contribute to the early inflammatory response to monosodium urate monohydrate (MSU) crystals in vivo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>MSU crystal\u2013induced inflammation was monitored using a peritoneal model of acute gout. The production of proinflammatory cytokines (interleukin\u20101\u03b2 [IL\u20101\u03b2], tumor necrosis factor \u03b1 [TNF\u03b1], IL\u20106) by resident macrophages, infiltrating monocytes, and neutrophils during the onset of gout was determined by flow cytometry. Infiltrating and resident peritoneal cells were cultured with MSU crystals ex vivo, and proinflammatory cytokine production was determined by multiplex cytokine array. Activated macrophages on the visceral epithelial lining of the peritoneum were identified by immunofluorescence histochemistry. The inflammatory immune response to MSU crystals was then compared with the inflammatory response in mice depleted of resident macrophages by pretreatment with clodronate liposomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The production of cytokines in vivo preceded the influx of Gr\u20101\n                      <jats:sup>intermediate<\/jats:sup>\n                      7\/4+ monocytes. Monocytes and neutrophils recruited during the inflammatory phase of the response to MSU crystals failed to produce proinflammatory cytokines either in vivo, or ex vivo following restimulation with MSU crystals. Stimulation of the naive peritoneal resident cell population with MSU crystals ex vivo resulted in positive staining of resident macrophages for the proinflammatory cytokines IL\u20101\u03b2, TNF\u03b1, and IL\u20106. Depletion of the resident macrophage population resulted in a significant decrease in both MSU crystal\u2013induced neutrophil infiltration and proinflammatory cytokine production in vivo despite the presence of infiltrating monocytes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These data indicate that resident macrophages, rather than infiltrating monocytes or neutrophils, are important for initiating and driving the early proinflammatory phase of acute gout.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.24185","type":"journal-article","created":{"date-parts":[[2008,12,31]],"date-time":"2008-12-31T16:41:14Z","timestamp":1230741674000},"page":"281-289","source":"Crossref","is-referenced-by-count":221,"title":["Resident macrophages initiating and driving inflammation in a monosodium urate monohydrate crystal\u2013induced murine peritoneal model of acute gout"],"prefix":"10.1002","volume":"60","author":[{"given":"William John","family":"Martin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela","family":"Walton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacquie","family":"Harper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,12,30]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780200320"},{"key":"e_1_2_6_3_2","first-page":"977","volume-title":"Inflammation: basic principles and clinical correlates","author":"Gordon T","year":"1988"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/anr.1780321114"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115142"},{"key":"e_1_2_6_6_2","doi-asserted-by":"crossref","first-page":"3213","DOI":"10.4049\/jimmunol.138.10.3213","article-title":"Interleukin 1 (IL 1) as a mediator of crystal arthritis: stimulation of T cell and synovial fibroblast mitogenesis by urate crystal\u2010induced IL 1","volume":"138","author":"Di Giovine FS","year":"1987","journal-title":"J Immunol"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.10326"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.20317"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.10614"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200008)43:8<1779::AID-ANR14>3.0.CO;2-2"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI28075"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04516"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.124.1.115"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.21633"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.9.5734"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M403823200"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0609.2002.02657.x"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.4.2336"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(96)00056-7"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI111380"},{"key":"e_1_2_6_21_2","first-page":"264","article-title":"The loss of macrophages from peritoneal exudates following the injection of antigens into guinea\u2010pigs with delayed\u2010type hypersensitivity","volume":"6","author":"Nelson DS","year":"1963","journal-title":"Immunology"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/0008-8749(85)90179-0"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/0008-8749(89)90367-5"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/38.9.818"}],"container-title":["Arthritis &amp; 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