title: Role of S100A8 and S100A9 in neutrophil recruitment in response to monosodium urate monohydrate crystals in the air-pouch model of acute gouty arthritis.
abstract: OBJECTIVE
  To examine the role of chemokines, S100A8, and S100A9 in neutrophil accumulation induced by the causative agent of gout, monosodium urate monohydrate (MSU) crystals.
  
  
  METHODS
  MSU crystal-induced neutrophil migration was studied in the murine air-pouch model. Release of chemokines, S100A8, S100A9, and S100A8/A9 in response to MSU crystals was quantified by enzyme-linked immunosorbent assays. Recruited cells were counted following acetic blue staining, and the subpopulations were characterized by Wright-Giemsa staining of cytospins.
  
  
  RESULTS
  MSU crystals induced the accumulation of neutrophils following injection in the air pouch, which correlated with the release of the chemokines CXCL1, CXCL2, CCL2, and CCL3. However, none of these was found to play an important role in neutrophil migration induced by MSU crystals by passive immunization with antibodies directed against each chemokine. S100A8, S100A9, and S100A8/A9 were also found at high levels in the pouch exudates following injection of MSU crystals. In addition, injection of S100A8, S100A9, or S100A8/A9 led to the accumulation of neutrophils in the murine air pouch, demonstrating their proinflammatory activities in vivo. Passive immunization with anti-S100A8 and anti-S100A9 led to a total inhibition of the accumulation of neutrophils. Finally, S100A8/A9 was found at high concentrations in the synovial fluid of patients with gout.
  
  
  CONCLUSIONS
  S100A8 and S100A8/A9 are essential to neutrophil migration induced by MSU crystals. These results suggest that they might be involved in the pathogenesis of gout.
authors.affiliation: Infectious Diseases Research Center, Centre de Recherche du Centre Hospitalier de l'Université Laval, 2705 Laurier Boulevard, Sainte-Foy, Quebec G1V 4G2, Canada.
authors.forename: Carle
authors.initials: C
authors.lastname: Ryckman
authors.forename: Shaun R
authors.initials: SR
authors.lastname: McColl
authors.forename: Karen
authors.initials: K
authors.lastname: Vandal
authors.forename: Rinaldo
authors.initials: R
authors.lastname: de Médicis
authors.forename: André
authors.initials: A
authors.lastname: Lussier
authors.forename: Patrice E
authors.initials: PE
authors.lastname: Poubelle
authors.forename: Philippe A
authors.initials: PA
authors.lastname: Tessier
mesh_terms: D000208:Acute Disease; D000388:Air; D000818:Animals; D000906:Antibodies; D015210:Arthritis, Gouty / Q000276:immunology* / Q000378:metabolism; D040501:Calgranulin A / Q000097:blood / Q000276:immunology*; D040502:Calgranulin B / Q000097:blood / Q000276:immunology*; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D018932:Chemokine CCL2 / Q000276:immunology / Q000378:metabolism; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D054360:Chemokine CXCL1; D018925:Chemokines / Q000276:immunology / Q000378:metabolism; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000276:immunology / Q000378:metabolism; D003460:Crystallization; D004195:Disease Models, Animal; D036341:Intercellular Signaling Peptides and Proteins / Q000276:immunology / Q000378:metabolism; D019402:Macrophage Inflammatory Proteins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000166:cytology / Q000276:immunology*; D013582:Synovial Fluid / Q000276:immunology / Q000378:metabolism; D014527:Uric Acid / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000906:Antibodies; D040501:Calgranulin A; D040502:Calgranulin B; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D054360:Chemokine CXCL1; D018925:Chemokines; D019743:Chemokines, CXC; D002630:Chemotactic Factors; C475895:Cxcl1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D019402:Macrophage Inflammatory Proteins; D014527:Uric Acid