Role of S100A8 and S100A9 in neutrophil recruitment in response to monosodium urate monohydrate crystals in the air-pouch model of acute gouty arthritis

Arthritis Rheum. 2003 Aug;48(8):2310-20. doi: 10.1002/art.11079.


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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Air
  • Animals
  • Antibodies
  • Arthritis, Gouty / immunology*
  • Arthritis, Gouty / metabolism
  • Calgranulin A / blood
  • Calgranulin A / immunology*
  • Calgranulin B / blood
  • Calgranulin B / immunology*
  • Cell Movement / drug effects
  • Cell Movement / immunology
  • Chemokine CCL2 / immunology
  • Chemokine CCL2 / metabolism
  • Chemokine CCL3
  • Chemokine CCL4
  • Chemokine CXCL1
  • Chemokines / immunology
  • Chemokines / metabolism
  • Chemokines, CXC*
  • Chemotactic Factors / immunology
  • Chemotactic Factors / metabolism
  • Crystallization
  • Disease Models, Animal
  • Intercellular Signaling Peptides and Proteins / immunology
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Macrophage Inflammatory Proteins / immunology
  • Macrophage Inflammatory Proteins / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Neutrophils / cytology
  • Neutrophils / immunology*
  • Synovial Fluid / immunology
  • Synovial Fluid / metabolism
  • Uric Acid / chemistry
  • Uric Acid / pharmacology*


  • Antibodies
  • Calgranulin A
  • Calgranulin B
  • Chemokine CCL2
  • Chemokine CCL3
  • Chemokine CCL4
  • Chemokine CXCL1
  • Chemokines
  • Chemokines, CXC
  • Chemotactic Factors
  • Cxcl1 protein, mouse
  • Intercellular Signaling Peptides and Proteins
  • Macrophage Inflammatory Proteins
  • Uric Acid