CELL ACIDIFICATION IN APOPTOSIS - GRANULOCYTE-COLONY-STIMULATING FACTOR DELAYS PROGRAMMED CELL-DEATH IN NEUTROPHILS BY UP-REGULATING THE VACUOLAR H-ATPASE()

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.