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

doi:10.1038/ni.2234

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

Department of Biotechnology

Research output: Contribution to journal › Article › peer-review

98 Citations (Scopus)

Abstract

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 language	English
Pages (from-to)	369-378
Number of pages	10
Journal	Nature Immunology
Volume	13
Issue number	4
DOIs	https://doi.org/10.1038/ni.2234
Publication status	Published - 2012 Apr

Bibliographical note

Funding Information:
We thank E. Tsitsikov, E. Rachlin, K. Imai and J. Yata for discussions; all patients who participated in this study; S. Goo Rhee (Ewha Womans University) for antibody to Prx1 phosphorylated at Tyr194; and J.A. Lindquist (Otto-von-Guericke University) for antibody to Cbp (PAG) phosphorylated at Tyr317. Supported by the Ministry of Health, Labour and Welfare of Japan (H. Kane, S.N. and T.M.), the Ministry of Education, Culture, Sports, Science and Technology of Japan (S.M. and T.M.) and by the National Research Foundation of Korea (National Creative Research Initiatives grant to S.-K.L.).

All Science Journal Classification (ASJC) codes

Immunology and Allergy
Immunology

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

abstract = "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.",

author = "Fumiko Honda and Hirotsugu Kano and Hirokazu Kanegane and Shigeaki Nonoyama and Kim, {Eun Sung} and Lee, {Sang Kyou} and Masatoshi Takagi and Shuki Mizutani and Tomohiro Morio",

note = "Funding Information: We thank E. Tsitsikov, E. Rachlin, K. Imai and J. Yata for discussions; all patients who participated in this study; S. Goo Rhee (Ewha Womans University) for antibody to Prx1 phosphorylated at Tyr194; and J.A. Lindquist (Otto-von-Guericke University) for antibody to Cbp (PAG) phosphorylated at Tyr317. Supported by the Ministry of Health, Labour and Welfare of Japan (H. Kane, S.N. and T.M.), the Ministry of Education, Culture, Sports, Science and Technology of Japan (S.M. and T.M.) and by the National Research Foundation of Korea (National Creative Research Initiatives grant to S.-K.L.).",

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AU - Kim, Eun Sung

AU - Lee, Sang Kyou

AU - Takagi, Masatoshi

AU - Mizutani, Shuki

AU - Morio, Tomohiro

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

Abstract

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