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Related Experiment Videos

Granzyme B: a natural born killer.

Sarah J Lord1, Ray V Rajotte, Gregory S Korbutt

  • 1Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.

Immunological Reviews
|May 20, 2003
PubMed
Summary
This summary is machine-generated.

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Cytotoxic T lymphocytes use granzyme B and perforin to induce apoptosis in target cells. Granzyme B initiates cell death through caspase activation and mitochondrial pathways, offering potential for cancer therapy.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells eliminate target cells via exocytosis of cytotoxic molecules.
  • Granzyme B and perforin are key cytolytic molecules that induce target cell DNA fragmentation and apoptosis.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which granzyme B induces apoptosis.
  • To explore the role of granzyme B in cell-mediated cytotoxicity and its therapeutic potential.

Main Methods:

  • The study describes the known pathway of granzyme B and perforin action.
  • It reviews the molecular interactions and signaling cascades involved in granzyme B-induced apoptosis.

Main Results:

Related Experiment Videos

  • Granzyme B is endocytosed via its receptor (mannose-6-phosphate/insulin-like growth factor II receptor) and released into the cytosol by perforin.
  • In the cytosol, granzyme B activates caspases directly or indirectly via mitochondria, leading to apoptosis.
  • Granzyme B also initiates mitochondrial events by cleaving Bid, even in the absence of caspase activity.
  • Release of apoptotic factors from mitochondria by granzyme B is crucial for full caspase-3 activation.

    • Conclusions:

    • Granzyme B acts at multiple intracellular points to initiate target cell apoptosis.
    • Understanding granzyme B signaling pathways may advance cell transplantation and cancer therapies.