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

Immunity. 2013 Feb 21;38(2):209-23. doi: 10.1016/j.immuni.2013.02.003.

Abstract

Regulated necrosis, termed necroptosis, is negatively regulated by caspase-8 and is dependent on the kinase activity of RIPK1 and RIPK3. Necroptosis leads to rapid plasma membrane permeabilization and to the release of cell contents and exposure of damage-associated molecular patterns (DAMPs). We are only beginning to identify the necroptotic DAMPs, their modifications, and their potential role in the regulation of inflammation. In this review, we discuss the physiological relevance of necroptosis and its role in the modulation of inflammation. For example, during viral infection, RIPK3-mediated necroptosis acts as a backup mechanism to clear pathogens. Necroptosis is also involved in apparently immunologically silent maintenance of T cell homeostasis. In contrast, the induction of necroptosis in skin, intestine, systemic inflammatory response syndrome, and ischemia reperfusion injury provoke a strong inflammatory response, which might be triggered by emission of DAMPs from necroptotic cells, showing the detrimental side of necroptosis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Apoptosis / immunology
  • Bacteria / growth & development
  • Bacterial Infections / immunology
  • Bacterial Infections / metabolism*
  • Bacterial Infections / physiopathology
  • Caspase 8 / genetics
  • Caspase 8 / immunology
  • Humans
  • Inflammation / immunology
  • Inflammation / metabolism*
  • Inflammation / physiopathology
  • Necrosis / immunology
  • Necrosis / metabolism*
  • Necrosis / physiopathology
  • Receptor-Interacting Protein Serine-Threonine Kinases / genetics
  • Receptor-Interacting Protein Serine-Threonine Kinases / immunology
  • Receptors, Pattern Recognition / genetics
  • Receptors, Pattern Recognition / immunology
  • Reperfusion Injury / immunology
  • Reperfusion Injury / metabolism*
  • Reperfusion Injury / physiopathology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Virus Diseases / immunology
  • Virus Diseases / metabolism*
  • Virus Diseases / physiopathology
  • Viruses / growth & development

Substances

  • Receptors, Pattern Recognition
  • RIPK1 protein, human
  • RIPK3 protein, human
  • Receptor-Interacting Protein Serine-Threonine Kinases
  • Caspase 8