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. 2003 Dec;17(15):2221-30.
doi: 10.1096/fj.03-0110com.

Macrophage migration inhibitory factor delays apoptosis in neutrophils by inhibiting the mitochondria-dependent death pathway

Ralf Baumann  1 , Carmen Casaulta, Dagmar Simon, Sébastien Conus, Shida Yousefi, Hans-Uwe Simon
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Macrophage migration inhibitory factor delays apoptosis in neutrophils by inhibiting the mitochondria-dependent death pathway

Ralf Baumann et al. FASEB J. 2003 Dec.

Abstract

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine known to activate macrophages and T cells VSports手机版. In this study, we demonstrate that recombinant MIF delays apoptosis of neutrophils in vitro. MIF action is dose and time dependent as well as specific since it was abolished with a neutralizing anti-MIF antibody. MIF, like G-CSF, delayed cleavage of the proapoptotic members of the Bcl-2 family Bid and Bax in neutrophils, suggesting that MIF inhibits apoptosis pathways proximal to mitochondria activation. Indeed, MIF also prevented release of cytochrome c and Smac from the mitochondria and subsequent activation of the critical effector caspase-3 in these cells. Moreover, we observed increased MIF plasma levels in patients with cystic fibrosis, a heterogeneous recessive genetic disorder associated with bacterial infections and delayed neutrophil apoptosis. In conclusion, MIF is a survival cytokine for human neutrophils, a finding with potential pathologic relevance in infectious diseases. .

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