Analysis of the mechanisms involved in the stimulation of neutrophil apoptosis by tumour necrosis factor-alpha.
We have previously reported that human neutrophils pretreated with tumour necrosis factor-alpha (TNF-alpha) and then exposed to a variety of agents such as immune complexes, zymosan, phorbol 12-myristate 13-acetate (PMA), C5a, fMLP, or granulocyte-macrophage colony-stimulating factor (GM-CSF), undergo a dramatic stimulation of apoptosis, suggesting that TNF-alpha is able to prime an apoptotic death programme which can be rapidly triggered by different stimuli. We report here that this response involves the participation of Mac-1 (CD11b/CD18), is dependent on caspases 3, 8 and 9, and is associated with both a loss of mitochondrial transmembrane potential and a down-regulation in expression of the anti-apoptotic protein, Mcl-1. Interestingly, we also found that the anti-apoptotic cytokine interleukin-1 (IL-1) improves the ability of TNF-alpha to promote apoptosis, supporting the notion than TNF-alpha, acting together with IL-1, may favour the depletion of neutrophils from the inflammatory areas during the course of acute inflammation.
Salamone
Gabriela
G
Institute of Hematologic Research, National Academy of Medicine, Buenos Aires, Argentina.
Trevani
Analía
A
Martínez
Diego
D
Vermeulen
Mónica
M
Gamberale
Romina
R
Fernández-Calotti
Paula
P
Raiden
Silvina
S
Giordano
Mirta
M
Geffner
Jorge
J
D017209:Apoptosis / Q000276:immunology*; D020169:Caspases / Q000276:immunology; D002478:Cells, Cultured; D015536:Down-Regulation / Q000276:immunology; D006801:Humans; D007375:Interleukin-1 / Q000276:immunology; D016177:Macrophage-1 Antigen / Q000276:immunology; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins / Q000276:immunology; D009504:Neutrophils / Q000276:immunology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D007375:Interleukin-1; D016177:Macrophage-1 Antigen; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D014409:Tumor Necrosis Factor-alpha; D020169:Caspases