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Granulocyte Colony-Stimulating Factor Upregulates the Vacuolar Proton ATPase in Human Neutrophils

Authors :
Hans Niessen
Beth S. Lee
Hai-Ling Li
Robert L. Engler
Barry Bowman
Stephen L. Gluck
Roberta A. Gottlieb
Grant W. Meisenholder
Bernard M. Babior
Source :
Blood. 90:4598-4601
Publication Year :
1997
Publisher :
American Society of Hematology, 1997.

Abstract

We have previously shown that granulocyte colony-stimulating factor (G-CSF ) delays spontaneous neutrophil apoptosis through activation of the vacuolar proton ATPase (v-ATPase). We have now examined the regulation of the v-ATPase in neutrophils exposed to G-CSF in vitro. When neutrophils were cultivated in the absence of G-CSF, the 57-kD cytosolic B subunit of the v-ATPase disappeared within 1 to 2 hours, its loss preceding the nuclear changes of apoptosis and coinciding with the onset of acidification. By contrast, in neutrophils cultured for 2 hours in the presence of G-CSF, the amount of the 57-kD subunit was similar to that in freshly isolated neutrophils. However, inhibition of protein synthesis with cycloheximide and actinomycin D led to loss of the 57-kD subunit even in the presence of G-CSF. These results indicated that ongoing protein synthesis was required to maintain the v-ATPase, and further suggested that G-CSF acted, at least in part, by maintaining synthesis of the 57-kD cytosolic subunit. G-CSF also promoted the translocation of the 57-and 33-kD cytosolic v-ATPase subunits to the membrane. Our findings suggested two coordinate mechanisms by which the activity of the v-ATPase could be increased by G-CSF: the synthesis of cytosolic v-ATPase subunits and their translocation to the membrane.

Details

ISSN :
15280020 and 00064971
Volume :
90
Database :
OpenAIRE
Journal :
Blood
Accession number :
edsair.doi.dedup.....10a52c4dd75be07710d46170ee7a0db9
Full Text :
https://doi.org/10.1182/blood.v90.11.4598.4598_4598_4601