Mekori Y A, Metcalfe D D
Department of Medicine, Meir Hospital Kfar-Saba, Tel-Aviv University, Israel.
J Immunol. 1994 Sep 1;153(5):2194-203.
IL-3-dependent mast cells undergo apoptosis upon removal of IL-3, an event that is prevented by the addition of stem cell factor (SCF) acting through its receptor c-kit, suggesting that SCF provides a mechanism to allow mast cells to survive and to differentiate in tissues in the relative absence of IL-3. This observation is consistent with the thesis that the microenvironment, in part, controls mast cell number and viability by modulating SCF production and release. The purpose of the present study was to determine whether a second factor, TGF-beta 1, was capable of modifying the SCF-mediated survival pathway. TGF-beta 1 (1 and 10 ng/ml), known to be an important regulator of cell growth and function, did inhibit the SCF-mediated rescue from apoptosis in IL-3-deprived mast cells. TGF-beta 1 exerted its inhibitory effect on SCF-mediated rescue from apoptosis, even when added 4 h after the addition of SCF. In contrast, TGF-beta 1 had no substantial effect on the viability of mast cells that were grown in the presence of IL-3. TGF-beta 1 also had no noticeable effect on viability and proliferation of a growth factor-independent mast cell line. The inhibitory effect of TGF-beta 1 was neutralized by specific anti-TGF-beta mAb. TGF-beta 1 did not affect the expression of c-kit, as determined by using flow cytometric analysis of mast cells labeled with FITC-conjugated anti-c-kit. These results demonstrate how SCF and TGF-beta may act in concert to regulate mast cell numbers under physiologic or pathologic conditions.
依赖白细胞介素-3的肥大细胞在去除白细胞介素-3后会发生凋亡，而添加通过其受体c-kit起作用的干细胞因子（SCF）可阻止这一事件，这表明SCF提供了一种机制，使肥大细胞能够在相对缺乏白细胞介素-3的组织中存活并分化。这一观察结果与以下观点一致，即微环境部分地通过调节SCF的产生和释放来控制肥大细胞的数量和活力。本研究的目的是确定第二种因子转化生长因子-β1（TGF-β1）是否能够改变SCF介导的存活途径。已知TGF-β1（1和10 ng/ml）是细胞生长和功能的重要调节因子，它确实抑制了SCF介导的对白细胞介素-3缺乏的肥大细胞凋亡的挽救作用。即使在添加SCF 4小时后添加，TGF-β1仍对SCF介导的凋亡挽救发挥抑制作用。相比之下，TGF-β1对在白细胞介素-3存在下生长的肥大细胞的活力没有实质性影响。TGF-β1对不依赖生长因子的肥大细胞系的活力和增殖也没有明显影响。TGF-β1的抑制作用被特异性抗TGF-β单克隆抗体中和。通过对用异硫氰酸荧光素（FITC）偶联的抗c-kit标记的肥大细胞进行流式细胞术分析确定，TGF-β1不影响c-kit的表达。这些结果证明了SCF和TGF-β如何协同作用以在生理或病理条件下调节肥大细胞数量。
