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The kinase Btk negatively regulates the production of reactive oxygen species and stimulation-induced apoptosis in human neutrophils

机译:激酶Btk负调节人类嗜中性粒细胞中活性氧的产生和刺激诱导的细胞凋亡

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The function of the kinase Btk in neutrophil activation is largely unexplored. Here we found that Btk-deficient neutrophils had more production of reactive oxygen species (ROS) after engagement of Toll-like receptors (TLRs) or receptors for tumor-necrosis factor (TNF), which was associated with more apoptosis and was reversed by transduction of recombinant Btk. Btk-deficient neutrophils in the resting state showed hyperphosphorylation and activation of phosphatidylinositol-3-OH kinase (PI(3)K) and protein tyrosine kinases (PTKs) and were in a 'primed' state with plasma membrane-associated GTPase Rac2. In the absence of Btk, the adaptor Mal was associated with PI(3)K and PTKs at the plasma membrane, whereas in control resting neutrophils, Btk interacted with and confined Mal in the cytoplasm. Our data identify Btk as a critical gatekeeper of neutrophil responses.
机译:激酶Btk在嗜中性粒细胞活化中的功能尚待探索。在这里,我们发现缺乏Btk的中性粒细胞在参与Toll样受体(TLRs)或肿瘤坏死因子(TNF)受体后具有更多的活性氧(ROS)产生,这与更多的细胞凋亡相关,并通过转导逆转重组Btk。处于静止状态的Btk缺乏中性粒细胞显示出过度磷酸化和磷脂酰肌醇3-OH激酶(PI(3)K)和蛋白酪氨酸激酶(PTKs)的激活,并且与质膜相关的GTPase Rac2处于“启动”状态。在没有Btk的情况下,衔接子Mal与质膜上的PI(3)K和PTK相关,而在对照静息的中性粒细胞中,Btk与Mal相互作用并将其限制在细胞质中。我们的数据表明Btk是嗜中性粒细胞反应的关键看门人。

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