Purinergic signaling, DAMPs, and inflammation

Am J Physiol Cell Physiol. 2020 May 1;318(5):C832-C835. doi: 10.1152/ajpcell.00053.2020. Epub 2020 Mar 11.

Abstract

Danger sensing is one of the most fundamental evolutionary features enabling multicellular organisms to perceive potential threats, escape from risky situations, fight actual intruders, and repair damage. Several endogenous molecules are used to "signal damage," currently referred to as "alarmins" or "damage-associated molecular patterns" (DAMPs), most being already present within all cells (preformed DAMPs), and thus ready to be released, and others neosynthesized following injury. Over recent years it has become overwhelmingly clear that adenosine 5'-triphosphate (ATP) is a ubiquitous and extremely efficient DAMP (thus promoting inflammation), and its main metabolite, adenosine, is a strong immunosuppressant (thus dampening inflammation). Extracellular ATP ligates and activates the P2 purinergic receptors (P2Rs) and is then degraded by soluble and plasma membrane ecto-nucleotidases to generate adenosine acting at P1 purinergic receptors (P1Rs). Extracellular ATP, P2Rs, ecto-nucleotidases, adenosine, and P1Rs are basic elements of the purinergic signaling network and fundamental pillars of inflammation.

Keywords: adenosine; extracellular ATP; inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / metabolism
  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphate / metabolism
  • Alarmins / genetics*
  • Alarmins / metabolism
  • Animals
  • Cell Membrane / metabolism
  • Humans
  • Immunosuppressive Agents / metabolism
  • Inflammation / metabolism*
  • Inflammation / physiopathology
  • Receptors, Purinergic P1 / genetics*
  • Receptors, Purinergic P2 / genetics*
  • Receptors, Purinergic P2 / metabolism
  • Signal Transduction / genetics

Substances

  • Alarmins
  • Immunosuppressive Agents
  • Receptors, Purinergic P1
  • Receptors, Purinergic P2
  • Adenosine Triphosphate
  • Adenosine Triphosphatases
  • ectoATPase
  • Adenosine