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ADAM17 activity during human neutrophil activation and apoptosis

Bruce Walcheck1, Amy H Herrera, Catherine St Hill

  • 1Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN 55108, USA. walch003@umn.edu

European Journal of Immunology
|March 17, 2006
PubMed

Insights

This study reveals that ADAM17 (TNF-alpha converting enzyme) remains active on human neutrophils during prolonged activation and apoptosis, influencing inflammatory responses.

Area of Science:

  • Immunology
  • Cell Biology
  • Protease Function

Background:

  • ADAM17 (TNF-alpha converting enzyme) mediates ectodomain shedding of inflammatory modulators.
  • Human neutrophil ADAM17 activity and regulation are poorly understood.
  • Existing research focuses on rapid ADAM17 activation, not prolonged function.

Purpose of the Study:

  • To investigate ADAM17 surface expression and substrate shedding in human neutrophils.
  • To examine ADAM17 activity during extended neutrophil activation and apoptosis.
  • To elucidate mechanisms regulating ADAM17 activity in neutrophils.

Main Methods:

  • Analysis of ADAM17 surface expression on human neutrophils.
  • Measurement of ADAM17 substrate shedding (L-selectin, proTNF-alpha).
  • Neutrophil activation via formyl peptides, FcR/complement receptors, and bacterial phagocytosis.
  • Induction of neutrophil apoptosis (spontaneous and anti-Fas).

Main Results:

  • ADAM17 surface expression is maintained on neutrophils during activation (formyl peptides, phagocytosis).
  • Bacterial phagocytosis significantly increased ADAM17 expression hours post-engulfment.
  • ADAM17 expression persisted during spontaneous and Fas-induced neutrophil apoptosis.
  • Efficient shedding of L-selectin and proTNF-alpha was observed under all tested conditions.

Conclusions:

  • Human neutrophils maintain prolonged ADAM17 expression during effector functions and apoptosis.
  • ADAM17 may play a dual role in both initiating and resolving neutrophil activity.
  • Findings challenge previous assumptions about ADAM17 regulation in neutrophils.

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