STIM1 calcium sensor is required for activation of the phagocyte oxidase during in flammation and host defense

Hong Zhang, Regina A. Clemens, Fengchun Liu, Yongmei Hu, Yoshihiro Baba, Pierre Theodore, Tomohiro Kurosaki, Clifford A. Lowell

研究成果: ジャーナルへの寄稿学術誌査読

64 被引用数 (Scopus)

抄録

The stromal-interactingmolecule 1 (STIM1) is a potent sensor of intracellular calcium, which in turn regulates entry of external calcium through plasmamembrane channels to affect immune cell activation. Although the contribution of STIM1 to calcium signaling in lymphocytes has been well studied, the role of this protein in neutrophil-mediated inflammation and host defense is unknown. We report that STIM1-deficient murine neutrophils show loss of store-operated calcium entry (SOCE) in response to both soluble ligands that activate G-proteins as well as Fcγ-receptor or integrin ligation that activates tyrosine kinase signaling. This results in modest defects in phagocytosis and degranulation responses but a profound block in superoxide production by the phagocyte oxidase. We trace the primary intracellular target of calcium to be protein kinase C isoforms α and β (PKCα and PKCβ), which in turn phosphorylate subunits of the oxidase leading to superoxide production. In vivo the loss of SOCE in stim1-/- chimeric mice results in marked susceptibility to bacterial infections but also protection from tissue injury in hepatic ischemia/reperfusion injury. These results demonstrate the critical role of STIM1-mediated SOCE and define major protein targets of calcium signaling in neutrophil activation during inflammatory disease.

本文言語英語
ページ(範囲)2238-2249
ページ数12
ジャーナルBlood
123
14
DOI
出版ステータス出版済み - 4月 3 2014
外部発表はい

!!!All Science Journal Classification (ASJC) codes

  • 生化学
  • 免疫学
  • 血液学
  • 細胞生物学

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