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The murine homolog of the interleukin-8 receptor CXCR-2 is essential for the occurrence of neutrophilic inflammation in the air pouch model of acute urate crystal-induced gouty synovitis

1998; Wiley; Volume: 41; Issue: 5 Linguagem: Inglês

10.1002/1529-0131(199805)41

1529-0131

Robert Terkeltaub, Stephen M. Baird, Peter Sears, Robert Santiago, William A. Boisvert,

Animal health and immunology

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 α [GROα]) 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/GROα 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/GROα 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.