Resident macrophages initiating and driving inflammation in a monosodium urate monohydrate crystal–induced murine peritoneal model of acute gout

作者：W. J. Martin, Michaela C. Walton, Jacquie L. Harper · 发表于：Arthritis & Rheumatism · 年份：2008 · DOI：10.1002/art.24185 · 被引用次数：255 · 研究领域：Gout, Hyperuricemia, Uric Acid、Kidney Stones and Urolithiasis Treatments、Thyroid Disorders and Treatments

OBJECTIVE: To determine whether infiltrating monocytes, neutrophils, or resident macrophages contribute to the early inflammatory response to monosodium urate monohydrate (MSU) crystals in vivo. METHODS: MSU crystal-induced inflammation was monitored using a peritoneal model of acute gout. The production of proinflammatory cytokines (interleukin-1beta [IL-1beta], tumor necrosis factor alpha [TNFalpha], IL-6) 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. RESULTS: The production of cytokines in vivo preceded the influx of Gr-1(intermediate)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 cytokin...