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

Fumiko Honda, Hirotsugu Kano, Hirokazu Kanegane, Shigeaki Nonoyama, Eun Sung Kim, Sang Kyou Lee, Masatoshi Takagi, Shuki Mizutani, Tomohiro Morio

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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.

Original languageEnglish
Pages (from-to)369-378
Number of pages10
JournalNature Immunology
Issue number4
Publication statusPublished - 2012 Apr 1


All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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