Apoptotic neutrophils release macrophage migration inhibitory factor upon stimulation with tumor necrosis factor-α

被引:33
作者
Daryadel, Arezoo [1 ]
Grifone, Remo Filippo [1 ]
Simon, Hans-Uwe [1 ]
Yousefi, Shida [1 ]
机构
[1] Univ Bern, Dept Pharmacol, CH-3010 Bern, Switzerland
关键词
D O I
10.1074/jbc.M604051200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:27653 / 27661
页数:9
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