Stat5 expression is critical for mast cell development and survival

Stat5 expression is critical for mast cell development and survival
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DOI:
10.1182/blood-2002-11-3490
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发表时间:
2003-08-15
期刊:
影响因子:
20.3
通讯作者:
Ryan, JJ
Ryan, JJ
中科院分区:
医学1区
文献类型:
--
作者:
Shelburne, CP;McCoy, ME;Ryan, JJ

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白细胞介素-3(IL-3)和干细胞因子(SCF)是肥大细胞生长和分化的重要因子。由于两种细胞因子;激活转录因子信号转导子和转录激活子5(Stat 5),一种已知的增殖和存活调节因子,我们研究了Stat 5缺陷对肥大细胞发育和存活的影响。从Stat 5A/B缺陷小鼠培养的骨髓源性肥大细胞(BMMC)群在IL-3 + SCF中存活,但在单独的细胞因子中不能存活。这些细胞在IL-3或SCIF培养期间表现出Bcl-2、Bcl-x(L)、细胞周期蛋白A2和细胞周期蛋白B1的表达减少,细胞凋亡增加并延迟细胞周期进程。最后,Stat 5的缺乏导致体内肥大细胞发育的丧失,如通过Stat 5缺陷小鼠和移植的评估所判断的。Stat 5缺陷型骨髓细胞移植给肥大细胞缺陷型受体小鼠。这些结果表明,Stat 5A和Stat 5 B是体外和体内肥大细胞发育和存活的关键调节因子。(C)2003年,美国血液学会。
Interleukin-3 (IL-3) and stem cell factor (SCF) are important mast cell growth and differentiation factors. Since both cytokines; activate the transcription factor signal transducer and activator of transcription 5 (Stat5), a known regulator of proliferation and survival, we investigated the effects of Stat5 deficiency on mast cell development and survival. Bone marrow-derived mast cell (BMMC) popu-lations cultured from Stat5A/B-deficient mice survived in IL-3 + SCF, but not in either cytokine alone. These cells demonstrated reduced expression of Bcl-2, Bcl-x(L), cyclin A2, and cyclin B1, with increased apoptosis and delayed cell cycle progression during IL-3 or SCIF culture. Finally, the absence of Stat5 resulted in loss of in vivo mast cell development, as judged by assessments of Stat5-deficient mice and transplantation. of Stat5-deficient bone marrow cells to mast cell-deficient recipient mice. These results indicate that Stat5A and Stat5B are critical regulators of in vitro and in vivo mast cell development and survival. (C) 2003 by The American Society of Hematology.