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In Vivo Treatment With Granulocyte Colony-Stimulating Factor Does Not Delay Apoptosis in Human Neutrophils by Increasing the Expression of the Vacuolar Proton ATPase
  1. Julie Zimbelman,
  2. Gail Thurman,
  3. Patrick J. Leavey,
  4. Misoo C. Ellison,
  5. Daniel R. Ambruso
  1. 1From the Bonfils Blood Center (J.Z., G.T., D.R.A.), University of Colorado School of MedicineDenver, Colo
  2. 2Department of Pediatrics, University of Colorado School of Medicine (J.Z., M.C.E., D.R.A.), Denver, Colo
  3. 3Department of Pediatrics, The Children's Hospital Research Institute (M.E., D.R.A.), Denver, Colo
  4. 4Department of Pediatrics, University of Texas Southwestern Medical Center (P.J.L.), Dallas, Tex.
  1. Address correspondence to: Daniel R. Ambruso, MD, Bonfils Blood Center, 717 Yosemite Street, Denver, CO 80230. E-mail daniel.ambruso{at}
  2. Supported by funds from the Bonfils Blood Center and the Stacy Marie True Memorial Trust.


Background Neutrophils die by apoptosis, and in vivo administration of granulocyte colony-stimulating factor (G-CSF) delays this apoptotic cell death. G-CSF administered in vitro correlates delayed apoptosis with upregulation of the vacuolar proton ATPase (v-ATPase). Because this enzyme requires assembly of membrane and cytosolic domains to function, we hypothesized that in vivo G-CSF would increase synthesis and assembly of v-ATPase components to delay apoptosis.

Methods Volunteers received G-CSF for 5 days, and each had a paired control. Neutrophils were isolated from subjects before the first and after the fifth injection. Proteins from cytosol or plasma membrane or from whole cell lysates were resolved by SDS-polyacrylamide gel electrophoresis and immunoblotted with antibody to the 33kDa v-ATPase E subunit. Densitometry quantified immunoreactivity.

Results No significant increase on the E subunit occurred between treated and control groups.

Conclusion In vivo G-CSF does not increase the amount of v-ATPase in neutrophils. Although G-CSF in vivo delays apoptosis, the mechanism(s) by which this occurs is not known.

Key Words
  • neutrophils
  • apoptosis
  • granulocyte colony-stimulating factor
  • cytokines
  • vacuolar ATPase

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