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 programmed 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 a...

Full description

Saved in:
Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1995-06, Vol.92 (13), p.5965-5968
Main Authors: Gottlieb, R A, Giesing, H A, Zhu, J Y, Engler, R L, Babior, B M
Format: Article
Language:English
Subjects:
Anti-Bacterial Agents - pharmacology
Apoptosis - drug effects
Cells, Cultured
Flow Cytometry
Granulocyte Colony-Stimulating Factor - pharmacology
Humans
Hydrogen-Ion Concentration
Kinetics
Macrolides
Neutrophils - cytology
Neutrophils - drug effects
Neutrophils - physiology
Proton-Translocating ATPases - antagonists & inhibitors
Proton-Translocating ATPases - blood
Vacuoles - enzymology
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Neutrophils in tissue culture spontaneously undergo programmed 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 A1, 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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.92.13.5965