The c-kit ligand, stem cell factor, promotes mast cell survival by suppressing apoptosis.
The c-kit ligand, stem cell factor, promotes mast cell survival by suppressing apoptosis.
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发表时间：
1994-02
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通讯作者：
A. Iemura;M. Tsai;A. Ando;B. Wershil;S. Galli
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作者：
A. Iemura;M. Tsai;A. Ando;B. Wershil;S. Galli
干细胞因子（SCF）及其受体（SCFR）是由c-kit基因编码的受体酪氨酸激酶III家族的成员，其关键调节几个复杂的生物学程序，包括造血、肥大细胞发育、皮肤色素沉着和配子发生。我们在此表明，小鼠肥大细胞死亡后迅速撤出SCF在体内或体外，并提供形态学证据表明，这种肥大细胞进行程序性细胞死亡或凋亡。我们还表明，当在体外衍生的小鼠肥大细胞维持在SCF从SCF的培养基中仅5或6小时，细胞的基因组DNA表现出典型的凋亡的梯状模式的染色体大小的片段。这些发现表明，SCF可以通过抑制细胞凋亡来调节表达SCFR的细胞谱系的存活。他们还确定了一种机制，可以导致组织肥大细胞群的大小显著和快速减少，而没有伴随诱导显著炎症反应的组织学证据。
Stem cell factor (SCF) and its receptor (SCFR), a member of the receptor tyrosine kinase III family that is encoded by the c-kit gene, critically regulate several complex biological programs including hematopoiesis, mast cell development, cutaneous pigmentation, and gametogenesis. We show herein that mouse mast cells die rapidly after the withdrawal of SCF in vivo or in vitro, and provide morphological evidence that such mast cells undergo programmed cell death or apoptosis. We also show that when in vitro-derived mouse mast cells maintained in SCF are removed from SCF-containing medium for only 5 or 6 hours, the cells' genomic DNA exhibits the ladder-like pattern of oligonucleosome-sized fragments typical of apoptosis. These findings demonstrate that SCF can regulate the survival of a cellular lineage which expresses the SCFR by suppressing apoptosis. They also identify a mechanism that can result in striking and rapid reductions in the size of tissue mast cell populations without histological evidence of the concomitant induction of a significant inflammatory response.