title: Interaction of tumor necrosis factor-alpha and granulocyte colony-stimulating factor on neutrophil apoptosis, receptor expression, and bactericidal function.
abstract: Infected patients are likely to have increased levels of tumor necrosis factor-alpha (TNF-alpha) and may be treated with recombinant human granulocyte colony-stimulating factor (G-CSF). Recombinant human TNF-alpha activates polymorphonuclear neutrophil (PMN) inflammatory activity. We examined the effect of exposure to TNF-alpha and G-CSF alone and in combination on PMN apoptosis, receptor expression, phagocytosis, and bactericidal function. The results were compared to those obtained with a promoter of PMN apoptosis, cycloheximide. After 24 hr, 27% of PMNs were nonapoptotic, and TNF-alpha (1 unit/ml) showed no change. Cycloheximide (10 micrograms/ml) decreased the number of nonapoptotic cells to 10% of the initial PMN. In contrast, G-CSF (30 ng/ml) decreased apoptosis (57% nonapoptotic PMN after 24 hr). Both G-CSF and TNF-alpha (but not cycloheximide) induced preservation of PMN Fc gamma RIII (467% and 167% of 24-hr controls, respectively) and beta 2-integrin expression (150% and 168% of 24-hr controls, respectively). G-CSF (but not TNF-alpha or cycloheximide) stimulated expression of Fc gamma RI (191% of 24-hr control) and Fc gamma RII (267% of 24-hr control). G-CSF (but not TNF-alpha) maintained the ability of PMN to ingest and kill opsonized Staphylococcus aureus. TNF-alpha decreased the effect of G-CSF on apoptosis, expression of Fc gamma RIII and Fc gamma RI, and bactericidal function. Thus, TNF-alpha promoted expression of Fc gamma RIII and beta 2-integrin receptors, which are important for phagocytic activity, and G-CSF diminished apoptosis, increased Fc gamma receptor expression, and maintained bactericidal function. TNF-alpha counteracted some effects of G-CSF. Interactions of these cytokines in vivo serve to regulate the PMN inflammatory response and bactericidal capacity.
authors.affiliation: Department of Medicine, University of Virginia, Charlottesville 22908, USA.
authors.forename: G W
authors.initials: GW
authors.lastname: Sullivan
authors.forename: A K
authors.initials: AK
authors.lastname: Gelrud
authors.forename: H T
authors.initials: HT
authors.lastname: Carper
authors.forename: G L
authors.initials: GL
authors.lastname: Mandell
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D002478:Cells, Cultured; D016179:Granulocyte Colony-Stimulating Factor / Q000502:physiology*; D006801:Humans; D018375:Neutrophil Activation / Q000502:physiology*; D009504:Neutrophils / Q000382:microbiology / Q000473:pathology / Q000502:physiology; D010587:Phagocytosis / Q000502:physiology; D013211:Staphylococcus aureus; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D016179:Granulocyte Colony-Stimulating Factor