Sensing necrotic cells

Adv Exp Med Biol. 2012;738:144-52. doi: 10.1007/978-1-4614-1680-7_9.

Abstract

Multicellular organisms have developed ways to recognize potentially life-threatening events (danger signals). Classically, danger signals have been defined as exogenous, pathogen-associated molecular patterns (PAMPs) such as bacterial cell wall components (e.g., lipopolysaccharide and peptideglycan) or viral DNA/RNA. PAMPs interact with dedicated receptors on immune cells, so-called pattern recognition receptors (PRRs) and activate immune systems. A well-known family of PRRs is the toll-like receptors (TLRs) in which each member recognizes a specific set of PAMPs. However, not only exogenous pathogens but also several endogenous molecules released from necrotic cells (damaged self) also activate immune systems. These endogenous adjuvants are called damage-associated molecular patterns (DAMPs). It has been reported that high-mobility group box 1 protein (HMGB1), uric acid, heat shock proteins (HSPs) and nucleotides act as endogenous adjuvants. DAMPs are recognized by specific receptors (danger receptors) expressed mainly on antigen-presenting cells such as dendritic cells and macrophages and induce cell maturation and the production of inflammatory cytokines by activating the NF-kB pathway. In this chapter, we will review danger signals released from necrotic cells and its recognition receptors.

Publication types

  • Review

MeSH terms

  • Animals
  • Bacteria / immunology
  • Cell Wall / immunology
  • Cytokines / immunology
  • DNA, Viral / immunology
  • Dendritic Cells / immunology*
  • Dendritic Cells / pathology
  • HMGB1 Protein / immunology
  • Humans
  • Immunity, Innate*
  • Lipopolysaccharides / immunology
  • Macrophages / immunology*
  • Macrophages / pathology
  • Necrosis / immunology*
  • Peptidoglycan / immunology
  • RNA, Viral / immunology
  • Signal Transduction / immunology*
  • Toll-Like Receptors / immunology
  • Viruses / immunology

Substances

  • Cytokines
  • DNA, Viral
  • HMGB1 Protein
  • Lipopolysaccharides
  • Peptidoglycan
  • RNA, Viral
  • Toll-Like Receptors