OBJECTIVE: Acute neutrophil-dependent inflammation is central to acute gout. Urate crystals induce different classes of neutrophil chemotaxins, including certain chemokines (e.g., interleukin-8 [IL-8], growth-related oncogene alpha [GROalpha]) that share CXCR-2 as a receptor. This study was undertaken to assess the role of CXCR-2 ligands in a model of acute gout. METHODS: Urate crystals were injected into subcutaneous air pouches in mice that expressed or lacked the murine CXCR-2 homolog (mIL-8RH), and the development of neutrophilic inflammation was assessed. RESULTS: In normal mice, urate crystals induced a 10-fold increase (P < 0.01) in pouch fluid leukocytes (principally neutrophils) at 4 hours. Leukocytes adhered to the pouch lining, where crystals, the mIL-8RH ligand KC/GROalpha, and cells bearing mIL-8RH were abundant. In mIL-8RH(-/-) mice, urate crystals induced a proteinaceous leukocyte-poor exudate at 4 hours, despite crystal-induced activation of resident cells (documented by KC/GROalpha expression). CONCLUSION: Chemokines that bind the IL-8 receptor CXCR-2 are essential for the development of acute neutrophilic inflammation in response to urate crystals in the subcutaneous air pouch model.
OBJECTIVE: Acute neutrophil-dependent inflammation is central to acute gout. Urate crystals induce different classes of neutrophil chemotaxins, including certain chemokines (e.g., interleukin-8 [IL-8], growth-related oncogene alpha [GROalpha]) that share CXCR-2 as a receptor. This study was undertaken to assess the role of CXCR-2 ligands in a model of acute gout. METHODS:Urate crystals were injected into subcutaneous air pouches in mice that expressed or lacked the murineCXCR-2 homolog (mIL-8RH), and the development of neutrophilic inflammation was assessed. RESULTS: In normal mice, urate crystals induced a 10-fold increase (P < 0.01) in pouch fluid leukocytes (principally neutrophils) at 4 hours. Leukocytes adhered to the pouch lining, where crystals, the mIL-8RH ligand KC/GROalpha, and cells bearing mIL-8RH were abundant. In mIL-8RH(-/-) mice, urate crystals induced a proteinaceous leukocyte-poor exudate at 4 hours, despite crystal-induced activation of resident cells (documented by KC/GROalpha expression). CONCLUSION: Chemokines that bind the IL-8 receptor CXCR-2 are essential for the development of acute neutrophilic inflammation in response to urate crystals in the subcutaneous air pouch model.
Authors: Richard A Colvin; Terry K Means; Thomas J Diefenbach; Luis F Moita; Robert P Friday; Sanja Sever; Gabriele S V Campanella; Tabitha Abrazinski; Lindsay A Manice; Catarina Moita; Norma W Andrews; Dianqing Wu; Nir Hacohen; Andrew D Luster Journal: Nat Immunol Date: 2010-05-16 Impact factor: 25.606
Authors: Christian Maueröder; Deborah Kienhöfer; Jonas Hahn; Christine Schauer; Bernhard Manger; Georg Schett; Martin Herrmann; Markus H Hoffmann Journal: J Mol Med (Berl) Date: 2015-05-24 Impact factor: 4.599