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Monosodium urate monohydrate crystals induce the release of the proinflammatory protein S100A8/A9 from neutrophils
C. Ryckman, C. Gilbert, R. Médicis, A. Lussier, Karen Vandal, P. Tessier
The neutrophil cytoplasmic protein S100A8/A9 (along with S100A8 and S100A9) is chemotactic and stimulates neutrophil adhesion by activating the β2‐integrin CD11b/CD18. It is also essential to neutrophil migration in vivo in response to monosodium ur…
The neutrophil cytoplasmic protein S100A8/A9 (along with S100A8 and S100A9) is chemotactic and stimulates neutrophil adhesion by activating the β2‐integrin CD11b/CD18. It is also essential to neutrophil migration in vivo in response to monosodium urate monohydrate (MSUM) crystals, the principal etiologic agent of gout. S100A8/A9 is present in the synovial fluid of patients with gout and arthritis and is secreted by activated monocytes; however, its mechanism of release by neutrophils remains unknown. The aim of this study was to identify the mechanism of stimulation of the release of S100A8/A9 by MSUM‐activated neutrophils. Here, we show that S100A8/A9 is released by neutrophils stimulated with MSUM crystals and that this release could be enhanced by preincubating neutrophils with granulocyte macrophage‐colony stimulating factor. Antibodies directed against CD11b and CD16 blocked the release induced by MSUM crystals, suggesting that Fc receptor for immunoglobulin G (FcγR)IIIB (CD16) and CD11b/CD18 were involved in the stimulation by MSUM crystals. Neutrophil preincubation with the Src kinase inhibitor 4‐amino‐5‐(4‐chlorophenyl)‐7‐(t‐butyl) pyrazolo[3,4‐d]pyrimidine and the Syk tyrosine kinase inhibitor trans‐3,3′,4,5′‐tetrahydrozystilbene significantly reduced the release of S100A8/A9, suggesting that the Src tyrosine kinase family and Syk were involved. In addition, wortmannin reduced neutrophil release of S100A8/A9, indicating a potential involvement of phosphatidylinolitol‐3 kinase in this release. Preincubation of neutrophils with the tubulin depolymerization promoters nocodazole and vincristine reduced MSUM‐induced release, suggesting a tubulin‐associated pathway of release. These results indicate that S100A8/A9 is released by MSUM crystal‐stimulated neutrophils following activation of CD11b, CD16, Src kinases, Syk, and tubulin polymerization.
Published in Journal of Leukocyte Biology
27
 6 2004