In vivo treatment with granulocyte colony-stimulating factor results in divergent effects on neutrophil functions measured in vitro.
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.
Leavey
P J
PJ
Bonfils Blood Center and the Departments of Pediatrics, Immunology and Biometrics, University of Colorado School of Medicine, Denver, CO, USA.
Sellins
K S
KS
Thurman
G
G
Elzi
D
D
Hiester
A
A
Silliman
C C
CC
Zerbe
G
G
Cohen
J J
JJ
Ambruso
D R
DR
D000328:Adult; D017209:Apoptosis / Q000187:drug effects; D018845:CD11 Antigens / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D018375:Neutrophil Activation / Q000187:drug effects*; D009504:Neutrophils / Q000187:drug effects* / Q000473:pathology / Q000502:physiology*
D018845:CD11 Antigens; D016179:Granulocyte Colony-Stimulating Factor; D002118:Calcium