Involvement of Bruton's tyrosine kinase in FcepsilonRI-dependent mast cell degranulation and cytokine production.
Involvement of Bruton's tyrosine kinase in FcepsilonRI-dependent mast cell degranulation and cytokine production.
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DOI：
10.1084/jem.187.8.1235
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发表时间：
1998-04-20
影响因子：
15.3
通讯作者：
Kawakami, T
中科院分区：
文献类型：
--
作者：
Hata, D;Kawakami, Y;Inagaki, N;Lantz, CS;Kitamura, T;Khan, WN;Maeda-Yamamoto, M;Miura, T;Han, W;Hartman, SE;Yao, L;Nagai, H;Goldfeld, AE;Alt, FW;Galli, SJ;Witte, ON;Kawakami, T
我们使用xid和btk缺失突变小鼠研究了布鲁顿酪氨酸激酶（Btk）在Fcε RI依赖性小鼠肥大细胞活化中的作用。与B细胞发育不同，肥大细胞发育在这些btk突变小鼠中明显正常。然而，来自这些小鼠的肥大细胞表现出Fcε RI依赖性功能的显著异常。用抗二硝基苯基单克隆IgE抗体致敏的xid小鼠在体内对抗原攻击的反应中表现出轻度减弱的早期过敏反应和严重减弱的晚期过敏反应。与这一发现一致，在FcεRI交联后，来自xid或btk缺失小鼠骨髓细胞的培养肥大细胞表现出脱颗粒的轻度损伤，以及几种细胞因子产生的更严重缺陷。此外，这些细胞因子基因的转录活性在Fcε RI刺激的btk突变型肥大细胞中严重降低。btk突变的这些效果的特异性被证实的btk突变体肥大细胞的能力，以determination和分泌细胞因子的逆转录病毒转移后的野生型btk cDNA，但不是载体或激酶死亡的btk cDNA的改善。逆转录病毒转移的Emt（= Itk/Tsk），Btk的最接近的亲戚，也部分提高了Btk突变肥大细胞分泌介质的能力。综上所述，这些结果表明Btk在肥大细胞中FcεRI信号转导的完全表达中起重要作用。
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.
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人肿瘤坏死因子α基因启动子中新型环孢菌素敏感元件的鉴定。
影响因子：
15.3
作者：
Goldfeld, A E;McCaffrey, P G;Strominger, J L;Rao, A
通讯作者：
Rao, A
DOI：
10.1073/pnas.89.19.9107
发表时间：
1992-10-01
影响因子：
11.1
作者：
HUTCHCROFT, JE;GEAHLEN, RL;OLIVER, JM
通讯作者：
OLIVER, JM
影响因子：
15.3
作者：
HAN, J;BROWN, T;BEUTLER, B
通讯作者：
BEUTLER, B
影响因子：
15.3
作者：
Cory, Giles O. C.;Lovering, Ruth C.;Hinshelwood, Steve;Maccarthy-Morrogh, Lucy;Levinsky, Roland J.;Kinnon, Christine
通讯作者：
Kinnon, Christine
DOI：
10.1073/pnas.91.20.9347
发表时间：
1994-09-27
影响因子：
11.1
作者：
AUGUST, A;GIBSON, S;DUPONT, B
通讯作者：
DUPONT, B