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

Arthritis Rheum. 1998 May;41(5):900-9. doi: 10.1002/1529-0131(199805)41:5<900::AID-ART18>3.0.CO;2-K.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute Disease
  • Animals
  • Arthritis, Gouty / chemically induced
  • Arthritis, Gouty / metabolism*
  • Arthritis, Gouty / pathology
  • Chemokines / metabolism
  • Crystallization
  • DNA Primers / chemistry
  • Disease Models, Animal
  • Female
  • Growth Substances / metabolism
  • Immunoenzyme Techniques
  • Ligands
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neutrophils / metabolism*
  • Polymerase Chain Reaction
  • Receptors, Chemokine / physiology*
  • Receptors, Interleukin / physiology*
  • Receptors, Interleukin-8B
  • Skin / drug effects
  • Synovitis / chemically induced
  • Synovitis / metabolism*
  • Synovitis / pathology

Substances

  • Chemokines
  • DNA Primers
  • Growth Substances
  • Ligands
  • Receptors, Chemokine
  • Receptors, Interleukin
  • Receptors, Interleukin-8B