CELL ACIDIFICATION IN APOPTOSIS - GRANULOCYTE-COLONY-STIMULATING FACTOR DELAYS PROGRAMMED CELL-DEATH IN NEUTROPHILS BY UP-REGULATING THE VACUOLAR H+-ATPASE
CELL ACIDIFICATION IN APOPTOSIS - GRANULOCYTE-COLONY-STIMULATING FACTOR DELAYS PROGRAMMED CELL-DEATH IN NEUTROPHILS BY UP-REGULATING THE VACUOLAR H+-ATPASE
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DOI：
10.1073/pnas.92.13.5965
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发表时间：
1995-06-20
影响因子：
11.1
通讯作者：
BABIOR, BM
中科院分区：
文献类型：
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作者：
GOTTLIEB, RA;GIESING, HA;BABIOR, BM
在组织培养中，中性粒细胞自发地经历程序性细胞死亡(凋亡)，这一过程的特征是影响细胞核的明确的形态变化。我们发现，这些形态变化发生在细胞内酸化之前，而粒细胞集落刺激因子(G-CSF)延迟了酸化和细胞核形态的凋亡性变化。在保护中性粒细胞免受细胞内酸化影响的药物中，有一种是空泡H+-ATPase，它能将质子从胞浆中抽出来。当这种质子泵被巴菲霉素抑制时，G-CSF不再保护中性粒细胞免于凋亡。我们的结论是，G-CSF通过上调中性粒细胞的空泡H+-ATPase来延迟中性粒细胞的凋亡，细胞内酸化是细胞凋亡过程中的一个早期事件。
Neutrophils in tissue culture spontaneously undergo programed cell death (apoptosis), a process characterized by well-defined morphological alterations affecting the cell nucleus. We found that these morphological changes were preceded by intracellular acidification and that acidification and the apoptotic changes in nuclear morphology were both delayed by granulocyte colony-stimulating factor (G-CSF). Among the agents that defend neutrophils against intracellular acidification is a vacuolar H+-ATPase that pumps protons out of the cytosol. When this proton pump was inhibited by bafilomycin At G-CSF no longer protected the neutrophils against apoptosis. We conclude that G-CSF delays apoptosis in neutrophils by up-regulating the cells' vacuolar H+-ATPase and that intracellular acidification is an early event in the apoptosis program.