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 defens e. G-CSF adversely affected neutrophil (polymorphonuclear leukocyte [P MN]) chemotaxis. While this could be partially explained by reduced as sembly 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 1 0:1 (bacteria: neutrophil) ratio and normal killing with a 1:1 ratio. In association with this, we demonstrated divergent effects on the res piratory burst of intact cells and divergent effects on the content of marker proteins for neutrophil granules. While G-CSF may have resulte d in increased content of cytochrome b(558) in the cell membrane, it d id not alter the amounts of cytosolic oxidase components. After therap y, there was normal content of the azurophilic granule marker, myelope roxidase, decreased content of the specific granule marker, lactoferri n, and normal content of lysozyme (found in both granules classes). Fi nally, G-CSF therapy markedly reduced the apoptotic rate of the isolat ed neutrophil. Therefore, considering disparate functional and biochem ical activities, the real benefit of G-CSF therapy may lie in enhanced number and survival of neutrophils. (C) 1998 by The American Society of Hematology.