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Necroptosis: the release of damage-associated molecular patterns and its physiological relevance

Agnieszka Kaczmarek1, Peter Vandenabeele, Dmitri V Krysko

  • 1Molecular Signaling and Cell Death Unit, Department for Molecular Biomedical Research, VIB, 9052 Ghent, Belgium.

Immunity
|February 27, 2013
PubMed

Insights

Necroptosis, a regulated form of necrosis, involves RIPK1 and RIPK3 kinases and releases damage-associated molecular patterns (DAMPs). This process can either clear pathogens or trigger harmful inflammation, depending on the context.

Area of Science:

  • Cellular Biology
  • Immunology
  • Molecular Biology

Background:

  • Necroptosis is a regulated form of necrosis.
  • It is negatively regulated by caspase-8.
  • It relies on the kinase activity of RIPK1 and RIPK3.

Purpose of the Study:

  • To review the physiological relevance of necroptosis.
  • To discuss necroptosis's role in modulating inflammation.
  • To explore damage-associated molecular patterns (DAMPs) released during necroptosis.

Main Methods:

  • Literature review of necroptosis.
  • Analysis of necroptosis's role in viral infections.
  • Examination of necroptosis's involvement in tissue injury and inflammation.

Main Results:

  • Necroptosis leads to plasma membrane permeabilization and DAMP release.
  • RIPK3-mediated necroptosis can act as a backup mechanism to clear pathogens during viral infections.
  • Necroptosis is implicated in T cell homeostasis maintenance.
  • Necroptosis in certain conditions (skin, intestine, SIRS, ischemia-reperfusion) provokes strong inflammatory responses due to DAMP emission.

Conclusions:

  • Necroptosis has a dual role: beneficial in pathogen clearance and homeostasis, but detrimental when inducing inflammation.
  • Further research is needed to fully identify necroptotic DAMPs and their inflammatory roles.
  • Understanding necroptosis is crucial for managing inflammatory diseases.

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