S100A9 potentiates the activation of neutrophils by the etiological agent of gout, monosodium urate crystals

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

Marceau, Franç¹  Paré¹  Fernandes, Maria¹  ois²  , Guillaume²  Pelletier, Martin³  Naccache, Paul H.³  Tessier, Philippe⁴  Lachhab, Asmaa⁴ 

[1] Department of Microbiology‐Infectious Diseases and Immunology, Faculty of Medicine, Laval University, Ville de Québec, Canada;bec, Qué

关键词: myeloid‐;    related protein;    signaling;    metabolism;    cytokines;   

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Gout is one of the most painful types of arthritis that arises when the body mounts an acute inflammatory reaction against a crystallized form of uric acid known as monosodium urate crystals (MSUs). Although MSUs are known to activate neutrophils, the most abundant leukocyte in the synovial fluid of patients with gout, few studies have investigated the effect on neutrophils of the simultaneous stimulation with MSU and proinflammatory mediators in the inflamed joint. Herein, we focused on a protein that is highly expressed in the synovium in gout, S100A9. The predominant expression of S100A9 in and around blood vessels suggests it may prime neutrophils during their migration toward the inflamed joint. Using a combination of functional and signaling assays, we found that S100A9 enhances the production of radical oxygen species as well as IL-1 and IL-8 release by human neutrophils activated with MSU. Moreover, upstream and downstream signaling events activated by MSUs in human neutrophils were also potentiated by S100A9, including the mobilization of intracellular calcium stores, tyrosine phosphorylation, the serine phosphorylation of PKC substrates, Akt, and p38. We also show that S100A9 alone increases glycolysis in human neutrophils, which is suggestive of an additional mechanism through which neutrophils can be primed. Together, our observations indicate a novel way in which S100A9 may contribute to the pathogenesis of gout, by priming neutrophils to respond to MSUs.

【 授权许可】

CC BY