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Blood, Vol. 92 No. 11 (December 1), 1998:
pp. 4366-4374
In Vivo Treatment With Granulocyte Colony-Stimulating Factor
Results in Divergent Effects on Neutrophil Functions Measured In
Vitro
Patrick J. Leavey,
Karen S. Sellins,
Gail Thurman,
David Elzi,
Andrew Hiester,
Christopher C. Silliman,
Gary Zerbe,
J. John Cohen, and
Daniel R. Ambruso
From the Bonfils Blood Center and the Departments of Pediatrics,
Immunology and Biometrics, University of Colorado School of Medicine,
Denver.
We have studied the effects of granulocyte colony-stimulating factor
(G-CSF) administration to normal individuals on a variety of functional
and biochemical neutrophil characteristics that relate to host defense.
G-CSF adversely affected neutrophil (polymorphonuclear leukocyte
[PMN]) chemotaxis. While this could be partially
explained by reduced assembly of neutrophil F-actin, we also recognized an elevated cytosolic calcium mobilization and a normal upregulation of
neutrophil CD11b. G-CSF resulted in reduced PMN killing of Staphylococcus aureus with a 10:1 (bacteria:neutrophil) ratio and
normal killing with a 1:1 ratio. In association with this, we
demonstrated divergent effects on the respiratory burst of intact cells
and divergent effects on the content of marker proteins for neutrophil
granules. While G-CSF may have resulted in increased content of
cytochrome b558 in the cell membrane, it did not alter the
amounts of cytosolic oxidase components. After therapy, there was
normal content of the azurophilic granule marker, myeloperoxidase, decreased content of the specific granule marker, lactoferrin, and
normal content of lysozyme (found in both granules classes). Finally,
G-CSF therapy markedly reduced the apoptotic rate of the isolated
neutrophil. Therefore, considering disparate functional and biochemical
activities, the real benefit of G-CSF therapy may lie in enhanced
number and survival of neutrophils.
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