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Cell death and cell lysis are separable events during pyroptosis

Lucian DiPeso1, Daisy X Ji1, Russell E Vance1,2

  • 1Division of Immunology & Pathogenesis, Department of Molecular & Cell Biology, and Cancer Research Laboratory, University of California, Berkeley, CA, USA.

Cell Death Discovery
|November 18, 2017
PubMed

Insights

Pyroptosis, a form of programmed cell death, involves distinct stages. This study reveals that cell death can occur independently of cell lysis, offering new insights into inflammasome activation control.

Area of Science:

  • Immunology
  • Cell Biology
  • Biochemistry

Background:

  • Inflammasome activation triggers pyroptosis, a lytic programmed cell death pathway.
  • The detailed temporal dynamics of pyroptosis's terminal phases remain incompletely understood.

Purpose of the Study:

  • To characterize the kinetics of pyroptosis in individual murine macrophages.
  • To investigate the relationship between cell death and cell lysis during pyroptosis.

Main Methods:

  • Utilized time-lapse fluorescence imaging for real-time observation of pyroptosis.
  • Analyzed individual murine macrophage behavior and cellular events.

Main Results:

  • Observed distinct sequential stages of cell death and subsequent cell lysis.
  • Demonstrated that gasdermin D pore formation leads to membrane permeability, cell movement cessation, mitochondrial dysfunction, and swelling.
  • Showed these events (death) can be decoupled from complete cell lysis.

Conclusions:

  • Proposed a model where pyroptosis-induced cell death can precede or occur independently of cell lysis.
  • Suggests this uncoupling mechanism may allow for regulated release of cytosolic contents during inflammasome activation.

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