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 language | English |
|---|---|
| Pages (from-to) | 1235-1247 |
| Number of pages | 13 |
| Journal | Journal of Experimental Medicine |
| Volume | 187 |
| Issue number | 8 |
| DOIs | |
| State | Published - Apr 20 1998 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Involvement of Bruton's tyrosine kinase in FcεRI-dependent mast cell degranulation and cytokine production
AU - Hata, Daisuke
AU - Kawakami, Yuko
AU - Inagaki, Naoki
AU - Lantz, Chris S.
AU - Kitamura, Toshio
AU - Khan, Wasif
AU - Maeda-Yamamoto, Mari
AU - Miura, Toru
AU - Han, Wei
AU - Hartman, Stephen E.
AU - Yao, Libo
AU - Nagai, Hiroichi
AU - Goldfeld, Anne E.
AU - Alt, Frederick W.
AU - Galli, Stephen J.
AU - Witte, Owen N.
AU - Kawakami, Toshiaki
PY - 1998/4/20
Y1 - 1998/4/20
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0032550335&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032550335&partnerID=8YFLogxK
U2 - 10.1084/jem.187.8.1235
DO - 10.1084/jem.187.8.1235
M3 - Article
VL - 187
SP - 1235
EP - 1247
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
SN - 0022-1007
IS - 8
ER -