Stat5a is essential for the proliferation and survival of murine mast cells
Stat5a is essential for the proliferation and survival of murine mast cells
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DOI：
10.1159/000085431
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发表时间：
2005-01-01
影响因子：
2.8
通讯作者：
Iwamoto, I
中科院分区：
文献类型：
--
作者：
Ikeda, K;Nakajima, H;Iwamoto, I
利用Stat 5a缺陷（Stat 5a-/-）小鼠测定信号转导子和转录激活子（Stat 5a）在肥大细胞增殖和存活中的调节作用。首先，虽然Stat 5a（-/-）小鼠中的肥大细胞在形态上与野生型（WT）小鼠中的肥大细胞无法区分，但与WT小鼠相比，Stat 5a-/-小鼠中的腹膜肥大细胞数量显著减少。此外，在Stat 5a（-/-）小鼠中，骨髓来源的肥大细胞（BMMCs）的白细胞介素-3（IL-3）依赖性发育显著减少。第二，与WT小鼠相比，Stat 5a-/-小鼠中IL-3诱导而非干细胞因子（SCF）诱导的BMMC增殖显著减少。此外，与WT小鼠相比，Stat 5a-/-小鼠的腹腔肥大细胞和BMMCs的存活率显著降低，凋亡细胞增加。IL-3刺激后WT BMMCs中Bcl-x（L）mRNA表达上调，而Stat 5a-/- BMMCs中Bcl-x（L）mRNA表达未上调，这可能是导致Stat 5a-/-肥大细胞凋亡加速的原因。这些结果表明Stat 5a在肥大细胞发育、增殖和存活中起重要作用。版权所有（C）2005 S. Karger AG，巴塞尔。
The regulatory role of signal transducer and activator of transcription (Stat) 5a in the proliferation and survival of mast cells was determined using Stat5a-deficient (Stat5a-/-) mice. First, although the mast cells in Stat5a(-/-) mice were morphologically indistinguishable from those in wild-type (WT) mice, the number of peritoneal mast cells was significantly decreased in Stat5a-/- mice as compared with that in WT mice. Furthermore, the interleukin-3 (IL-3)-dependent development of bone marrow-derived mast cells (BMMCs) was markedly decreased in Stat5a(-/-) mice. Second, IL-3-induced but not stem cell factor (SCF)-induced proliferation of BMMCs was significantly diminished in Stat5a-/- mice as compared with that in WT mice. Moreover, survival rates of both peritoneal mast cells and BMMCs were significantly decreased with increased apoptotic cells in Stat5a-/- mice as compared with those in WT mice. Finally, mRNA of Bcl-x(L) was induced after IL-3 stimulation in WT BMMCs but not in Stat5a-/- BMMCs, which may account for the accelerated apoptosis in Stat5a-/- mast cells. These results indicate that Stat5a plays an important role in mast cell development, proliferation, and survival. Copyright (C) 2005 S. Karger AG, Basel.