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Neutrophil superoxide release is required for spontaneous and FMLP-mediated but not for TNF alpha-mediated apoptosis

R Kettritz1, R J Falk, J C Jennette

  • 1Department of Medicine, University of North Carolina at Chapel Hill 27599-7155, USA.

Journal of the American Society of Nephrology : JASN
|July 1, 1997
PubMed

Insights

Polymorphonuclear leukocyte (PMN) apoptosis mechanisms were studied. Superoxide release drives PMN aging and FMLP-stimulated apoptosis, but not TNF-alpha-induced cell death.

Area of Science:

  • Immunology
  • Cell Biology
  • Biochemistry

Background:

  • Polymorphonuclear leukocytes (PMNs) have short lifespans, involving rapid production and programmed cell death (apoptosis).
  • The precise triggers for PMN apoptosis remain incompletely understood.
  • Investigating the role of neutrophil activation and superoxide release in PMN apoptosis is crucial.

Purpose of the Study:

  • To investigate the relationship between neutrophil activation, superoxide release, and apoptosis in polymorphonuclear leukocytes.
  • To determine the specific pathways involved in TNF-alpha and FMLP-induced PMN apoptosis.
  • To elucidate the role of superoxide in PMN aging and programmed cell death.

Main Methods:

  • PMN apoptosis was assessed using DNA fragmentation, microscopy, and flow cytometry.
  • Superoxide release was quantified via superoxide dismutase-inhibitable reduction of ferricytochrome C.
  • Gene expression of manganese superoxide dismutase was analyzed using reverse transcription PCR.

Main Results:

  • Tumor necrosis factor-alpha (TNF-alpha) induced both superoxide release and apoptosis in PMNs.
  • FMLP stimulation led to significant superoxide release and increased apoptosis at 24 hours.
  • Exogenous superoxide dismutase inhibited FMLP-induced and aging-related PMN apoptosis, but not TNF-alpha-induced apoptosis.

Conclusions:

  • PMN apoptosis during aging and FMLP stimulation is dependent on superoxide release.
  • TNF-alpha-facilitated PMN apoptosis occurs independently of respiratory burst oxidase activity.
  • Understanding these distinct pathways is key to modulating PMN lifespan and inflammatory responses.

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