Promotion of neutrophil apoptosis by TNF-alpha.
We examined the ability of TNF-alpha to modulate human neutrophil apoptosis. Neutrophils cultured with TNF-alpha alone undergo a low but significant increase in the number of apoptotic cells. More interestingly, when neutrophils were pretreated with TNF-alpha for 1-2 min at 37 degrees C and then were exposed to a variety of agents such as immobilized IgG, IgG-coated erythrocytes, complement-treated erythrocytes, zymosan, PMA, zymosan-activated serum, fMLP, Escherichia coli, and GM-CSF for 3 h at 37 degrees C, a marked stimulation of apoptosis was observed. Similar results were obtained in neutrophils pretreated with TNF-alpha for 30 min, 1 h, 3 h, and 18 h. Dose-dependent studies showed that TNF-alpha enhances neutrophil apoptosis at concentrations ranging from 1 to 100 ng/ml. In contrast to the observations made in neutrophils pretreated with TNF-alpha, there was no stimulation of apoptosis when TNF-alpha was added to neutrophils previously activated by conventional agonists. Experiments performed to establish the mechanism through which TNF-alpha promotes neutrophil apoptosis showed that neither reactive oxygen intermediates nor the Fas/Fas ligand system appear to be involved. Our results suggest that TNF-alpha plays a critical role in the control of neutrophil survival by virtue of its ability to induce an apoptotic death program which could be triggered by a variety of conventional agonists.
Salamone
G
G
Laboratory of Immunology, Institute of Hematologic Research, National Academy of Medicine, Buenos Aires, Argentina. geffner@mail.retina.ar
Giordano
M
M
Trevani
A S
AS
Gamberale
R
R
Vermeulen
M
M
Schettinni
J
J
Geffner
J R
JR
D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000276:immunology*; D001769:Blood / Q000276:immunology; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000502:physiology; D004306:Dose-Response Relationship, Immunologic; D053222:Fas Ligand Protein; D006801:Humans; D007399:Interphase / Q000276:immunology; D008024:Ligands; D008562:Membrane Glycoproteins / Q000502:physiology; D009504:Neutrophils / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D010718:Phosphatidylserines / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D017382:Reactive Oxygen Species / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D019014:fas Receptor / Q000502:physiology
D017304:Annexin A5; D017077:Culture Media, Conditioned; D016207:Cytokines; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008024:Ligands; D008562:Membrane Glycoproteins; D010718:Phosphatidylserines; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor