Involvement of Bruton's tyrosine kinase in FcεRI-dependent mast cell degranulation and cytokine production

Daisuke Hata, Yuko Kawakami, Naoki Inagaki, Chris S. Lantz, Toshio Kitamura, Wasif Khan, Mari Maeda-Yamamoto, Toru Miura, Wei Han, Stephen E. Hartman, Libo Yao, Hiroichi Nagai, Anne E. Goldfeld, Frederick W. Alt, Stephen J. Galli, Owen N. Witte, Toshiaki Kawakami

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Abstract

We investigated the role of Bruton's tyrosine kinase (Btk) in FcεRI- dependent activation of mouse mast cells, using xid and btk null mutant mice. Unlike B cell development, mast cell development is apparently normal in these btk mutant mice. However, mast cells derived from these mice exhibited significant abnormalities in FcεRI-dependent function. xid mice primed with anti-dinitrophenyl monoclonal IgE antibody exhibited mildly diminished early- phase and severely blunted late-phase anaphylactic reactions in response to antigen challenge in vivo. Consistent with this finding, cultured mast cells derived from the bone marrow cells of xid or btk null mice exhibited mild impairments in degranulation, and more profound defects in the production of several cytokines, upon FcεRI cross-linking. Moreover, the transcriptional activities of these cytokine genes were severely reduced in FcεRI-stimulated btk mutant mast cells. The specificity of these effects of btk mutations was confirmed by the improvement in the ability of btk mutant mast cells to degranulate and to secrete cytokines after the retroviral transfer of wild- type btk cDNA, but not of vector or kinase-dead btk cDNA. Retroviral transfer of Emt (= Itk/Tsk), Btk's closest relative, also partially improved the ability of btk mutant mast cells to secrete mediators. Taken together, these results demonstrate an important role for Btk in the full expression of FcεRI signal transduction in mast cells.

Original languageEnglish
Pages (from-to)1235-1247
Number of pages13
JournalJournal of Experimental Medicine
Volume187
Issue number8
DOIs
StatePublished - Apr 20 1998
Externally publishedYes

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Cell Degranulation
Mast Cells
Cytokines
Complementary DNA
Agammaglobulinaemia tyrosine kinase
Anaphylaxis
Bone Marrow Cells
Immunoglobulin E
Cultured Cells
Signal Transduction
B-Lymphocytes
Phosphotransferases
Monoclonal Antibodies
Antigens
Mutation

ASJC Scopus subject areas

  • Immunology

Cite this

Involvement of Bruton's tyrosine kinase in FcεRI-dependent mast cell degranulation and cytokine production. / Hata, Daisuke; Kawakami, Yuko; Inagaki, Naoki; Lantz, Chris S.; Kitamura, Toshio; Khan, Wasif; Maeda-Yamamoto, Mari; Miura, Toru; Han, Wei; Hartman, Stephen E.; Yao, Libo; Nagai, Hiroichi; Goldfeld, Anne E.; Alt, Frederick W.; Galli, Stephen J.; Witte, Owen N.; Kawakami, Toshiaki.

In: Journal of Experimental Medicine, Vol. 187, No. 8, 20.04.1998, p. 1235-1247.

Research output: Contribution to journalArticle

Hata, D, Kawakami, Y, Inagaki, N, Lantz, CS, Kitamura, T, Khan, W, Maeda-Yamamoto, M, Miura, T, Han, W, Hartman, SE, Yao, L, Nagai, H, Goldfeld, AE, Alt, FW, Galli, SJ, Witte, ON & Kawakami, T 1998, 'Involvement of Bruton's tyrosine kinase in FcεRI-dependent mast cell degranulation and cytokine production', Journal of Experimental Medicine, vol. 187, no. 8, pp. 1235-1247. https://doi.org/10.1084/jem.187.8.1235
Hata, Daisuke ; Kawakami, Yuko ; Inagaki, Naoki ; Lantz, Chris S. ; Kitamura, Toshio ; Khan, Wasif ; Maeda-Yamamoto, Mari ; Miura, Toru ; Han, Wei ; Hartman, Stephen E. ; Yao, Libo ; Nagai, Hiroichi ; Goldfeld, Anne E. ; Alt, Frederick W. ; Galli, Stephen J. ; Witte, Owen N. ; Kawakami, Toshiaki. / Involvement of Bruton's tyrosine kinase in FcεRI-dependent mast cell degranulation and cytokine production. In: Journal of Experimental Medicine. 1998 ; Vol. 187, No. 8. pp. 1235-1247.
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AU - Kitamura, Toshio

AU - Khan, Wasif

AU - Maeda-Yamamoto, Mari

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AU - Yao, Libo

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AU - Goldfeld, Anne E.

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