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Detection of Inflammasome Activation and Pyroptotic Cell Death in Murine Bone Marrow-derived Macrophages
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Inflammasome Activation Triggers Blood Clotting and Host Death through Pyroptosis

Congqing Wu1, Wei Lu2, Yan Zhang1

  • 1Saha Cardiovascular Research Center, College of Medicine, University of Kentucky, Lexington, KY, USA.

Immunity
|May 12, 2019
PubMed

Insights

Inflammasome activation triggers blood clotting via pyroptosis, leading to host death. Inhibiting tissue factor stops this inflammasome-driven thrombosis and protects against fatality.

Area of Science:

  • Immunology
  • Pathology
  • Microbiology

Background:

  • Inflammasomes are crucial for microbial defense but overactivation causes host death.
  • Pyroptosis, a form of inflammatory cell death, follows inflammasome activation.
  • The role of pyroptosis in host death and pathogenesis remains unclear.

Purpose of the Study:

  • To investigate the link between inflammasome activation, pyroptosis, and host death.
  • To elucidate the mechanism by which pyroptotic cell death drives pathogenesis.
  • To identify inflammasome activation as a trigger for blood clotting.

Main Methods:

  • Studied canonical inflammasome activation by type III secretion system (T3SS) rod proteins.
  • Investigated noncanonical inflammasome activation by lipopolysaccharide (LPS).
  • Analyzed pyroptotic macrophage release of tissue factor (TF) and its role in coagulation.

Main Results:

  • Inflammasome activation, via T3SS or LPS, induced systemic blood clotting and thrombosis.
  • Pyroptotic macrophages released TF, initiating coagulation cascades.
  • Inhibiting TF abolished inflammasome-mediated clotting and protected against death.

Conclusions:

  • Blood clotting is the primary cause of host death following inflammasome activation.
  • Inflammasome activation bridges inflammation and thrombosis.
  • Targeting TF offers a protective strategy against inflammasome-induced mortality.
Keywords:
DICGSDMDLPScaspasecoagulationinflammasomemacrophagepyroptosissepsistissue factor

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