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.
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).


CONCLUSIONS
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.
Terkeltaub
R
R
San Diego VA Medical Center and University of California, 92161, USA.
Baird
S
S
Sears
P
P
Santiago
R
R
Boisvert
W
W
D000208:Acute Disease; D000818:Animals; D015210:Arthritis, Gouty / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D018925:Chemokines / Q000378:metabolism; D003460:Crystallization; D017931:DNA Primers / Q000737:chemistry; D004195:Disease Models, Animal; D005260:Female; D006133:Growth Substances / Q000378:metabolism; D007124:Immunoenzyme Techniques; D008024:Ligands; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D019707:Receptors, Chemokine / Q000502:physiology*; D018123:Receptors, Interleukin / Q000502:physiology*; D023063:Receptors, Interleukin-8B; D012867:Skin / Q000187:drug effects; D013585:Synovitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology
D018925:Chemokines; D017931:DNA Primers; D006133:Growth Substances; D008024:Ligands; D019707:Receptors, Chemokine; D018123:Receptors, Interleukin; D023063:Receptors, Interleukin-8B