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

Arezoo Daryadel1, Remo Filippo Grifone, Hans-Uwe Simon

  • 1Department of Pharmacology, University of Bern, CH-3010 Bern, Switzerland.

The Journal of Biological Chemistry
|July 25, 2006
PubMed

Insights

Mature neutrophils release macrophage migration inhibitory factor (MIF) during apoptosis, a process influenced by tumor necrosis factor-alpha. This cytokine release suggests inflammation can occur even as cells undergo programmed cell death.

Area of Science:

  • Immunology
  • Cell Biology

Background:

  • Macrophage migration inhibitory factor (MIF) is a key cytokine in innate immunity, with elevated levels during inflammation.
  • Neutrophils are crucial immune cells involved in inflammatory responses.

Purpose of the Study:

  • To investigate the expression and release of MIF from mature neutrophils during apoptosis.
  • To determine the mechanisms regulating MIF release from apoptotic neutrophils.

Main Methods:

  • Analysis of MIF expression in neutrophils.
  • Induction of neutrophil apoptosis using tumor necrosis factor-alpha (TNF-alpha).
  • Assessment of MIF release and its dependence on caspases and ATP-binding cassette transporters.

Main Results:

  • Mature neutrophils constitutively express MIF as a cytosolic protein.
  • Apoptotic neutrophils release functional MIF in a caspase-dependent manner upon TNF-alpha stimulation.
  • MIF release occurs before phagocytosis and is inhibited by glyburide and propenicide, implicating ABC transporters.

Conclusions:

  • Apoptotic neutrophils can actively release MIF, a pro-inflammatory cytokine.
  • TNF-alpha-induced MIF release from apoptotic neutrophils involves caspase activation and ABC transporter activity.
  • Neutrophil apoptosis may contribute to inflammatory processes rather than solely resolving them.

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