Apoptotic neutrophils release macrophage migration inhibitory factor upon stimulation with tumor necrosis factor-alpha.
Macrophage migration inhibitory factor (MIF) is an important cytokine involved in the regulation of innate immunity and present at increased levels during inflammatory responses. Here we demonstrate that mature blood and tissue neutrophils constitutively express MIF as a cytosolic protein not associated with azurophil granules. Functionally active MIF, but not proteases stored in azurophil granules, was released from apoptotic neutrophils following short term tumor necrosis factor (TNF)-alpha stimulation in a caspase-dependent manner and prior to any detectable phagocytosis by monocyte-derived macrophages. Moreover, TNF-alpha-mediated MIF release was blocked by glyburide and propenicide, both inhibitors of ATP-binding cassette-type transporters, suggesting that this transporter system is activated during neutrophil apoptosis. Taken together, apoptotic mature neutrophils release MIF upon short term TNF-alpha stimulation. Therefore, apoptosis may not always occur without the induction of pro-inflammatory mechanisms.
Daryadel
Arezoo
A
Department of Pharmacology, University of Bern, CH-3010 Bern, Switzerland.
Grifone
Remo Filippo
RF
Simon
Hans-Uwe
HU
Yousefi
Shida
S
D000255:Adenosine Triphosphate / Q000737:chemistry; D017209:Apoptosis; D002630:Chemotactic Factors / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D008263:Macrophage Migration-Inhibitory Factors / Q000378:metabolism*; D008264:Macrophages; D018613:Microscopy, Confocal; D009000:Monocytes / Q000201:enzymology; D009504:Neutrophils / Q000378:metabolism* / Q000473:pathology*; D010587:Phagocytosis; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D002630:Chemotactic Factors; D008263:Macrophage Migration-Inhibitory Factors; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000255:Adenosine Triphosphate