Elsevier

Cellular Immunology

Volume 195, Issue 1, 10 July 1999, Pages 43-52
Cellular Immunology

Regular Article
Reduction in Mitochondrial Membrane Potential Is an Early Event in Fas-Independent CTL-Mediated Apoptosis

https://doi.org/10.1006/cimm.1999.1513Get rights and content

Abstract

Cytotoxic T lymphocytes (CTL) can destroy target cells via the Fas-mediated pathway or the granule-mediated pathway. We used Fas-negative target cells to examine for target-cell reduction in mitochondrial membrane potential (ΔΨm) induced by intact CTL via the granule-mediated pathway. We find that reduction in ΔΨm is an early step in Fas-independent CTL killing of target cells that precedes phosphatidyl serine translocation, cytosolic protein release, or loss of plasma membrane integrity. Target-cell reduction in ΔΨm and cytoplasmic protein release in Fas-independent CTL killing were inhibited by N-carbobenzoxy-Ala-Pro-Phe chloromethyl ketone, but not by caspase inhibitors N-carbobenzoxy-Val-Ala-Asp fluoromethyl ketone (z-VAD-fmk) or N-carbobenzoxy-Asp-Glu-Val-Asp fluoromethyl ketone (z-DEVD-fmk). This contrasts with Fas-mediated apoptosis, in which the reduction in ΔΨm can be inhibited by z-VAD-fmk or z-DEVD-fmk. Assessing the changes in target-cell ΔΨm can provide for a sensitive and rapid means with which to monitor CTL activity.

References (42)

  • C.J. Froelich et al.

    Immunol. Today

    (1998)
  • M.D. Jacobson et al.

    Cell

    (1997)
  • S. Nagata

    Cell

    (1997)
  • P.A. Henkart

    Immunity

    (1996)
  • G. Berke

    Cell

    (1995)
  • M.G. Vander Heiden et al.

    Cell

    (1997)
  • A. Sarin et al.

    Immunity

    (1997)
  • J.W. Heusel et al.

    Cell

    (1994)
  • N.A. Thornberry et al.

    J. Biol. Chem.

    (1997)
  • F. Andrade et al.

    Immunity

    (1998)
  • H. Li et al.

    J. Biol. Chem.

    (1997)
  • A.M. Chinnaiyan et al.

    Curr. Biol.

    (1996)
  • X. Liu et al.

    Cell

    (1996)
  • P.X. Petit et al.

    FEBS Lett.

    (1996)
  • J.C. Reed

    Cell

    (1997)
  • V.P. Skulachev

    FEBS Let.

    (1996)
  • J.G. Pastorino et al.

    J. Biol. Chem.

    (1998)
  • G. Kroemer et al.

    Immunol. Today

    (1997)
  • H.M. Korchak et al.

    Biochem. Biophys. Res. Commun.

    (1982)
  • I. Vermes et al.

    J. Immunol. Methods

    (1995)
  • Cited by (0)

    View full text