CELL ACIDIFICATION IN APOPTOSIS - GRANULOCYTE-COLONY-STIMULATING FACTOR DELAYS PROGRAMMED CELL-DEATH IN NEUTROPHILS BY UP-REGULATING THE VACUOLAR H-ATPASE()
Ra. Gottlieb et al., CELL ACIDIFICATION IN APOPTOSIS - GRANULOCYTE-COLONY-STIMULATING FACTOR DELAYS PROGRAMMED CELL-DEATH IN NEUTROPHILS BY UP-REGULATING THE VACUOLAR H-ATPASE(), Proceedings of the National Academy of Sciences of the United Statesof America, 92(13), 1995, pp. 5965-5968
Neutrophils in tissue culture spontaneously undergo programed cell dea
th (apoptosis), a process characterized by well-defined morphological
alterations affecting the cell nucleus. We found that these morphologi
cal changes were preceded by intracellular acidification and that acid
ification and the apoptotic changes in nuclear morphology were both de
layed by granulocyte colony-stimulating factor (G-CSF). Among the agen
ts that defend neutrophils against intracellular acidification is a va
cuolar H+-ATPase that pumps protons out of the cytosol. When this prot
on 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 tha
t intracellular acidification is an early event in the apoptosis progr
am.