Abscisic acid is an endogenous cytokine in human granulocytes with cyclic ADP-ribose as second messenger

Proc Natl Acad Sci U S A. 2007 Apr 3;104(14):5759-64. doi: 10.1073/pnas.0609379104. Epub 2007 Mar 26.


Abscisic acid (ABA) is a phytohormone involved in fundamental physiological processes of higher plants, such as response to abiotic stress (temperature, light, drought), regulation of seed dormancy and germination, and control of stomatal closure. Here, we provide evidence that ABA stimulates several functional activities [phagocytosis, reactive oxygen species and nitric oxide (NO) production, and chemotaxis] of human granulocytes through a signaling pathway sequentially involving a pertussis toxin (PTX)-sensitive G protein/receptor complex, protein kinase A activation, ADP-ribosyl cyclase phosphorylation, and consequent cyclic-ADP-ribose overproduction, leading to an increase of the intracellular Ca(2+) concentration. The increase of free intracellular ABA and its release by activated human granulocytes indicate that ABA should be considered as a new pro-inflammatory cytokine in humans. This discovery is an intriguing example of conservation of a hormone and its signaling pathway from plants to humans and provides insight into the molecular mechanisms of granulocyte activation, possibly leading to the development of new antiinflammatory drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abscisic Acid / metabolism*
  • Abscisic Acid / pharmacology
  • Calcium Signaling / drug effects
  • Calcium Signaling / physiology
  • Cells, Cultured
  • Chemotaxis / drug effects
  • Chemotaxis / physiology
  • Cyclic ADP-Ribose / analysis
  • Cyclic ADP-Ribose / metabolism*
  • Cytokines / metabolism*
  • Dose-Response Relationship, Drug
  • Granulocytes / drug effects
  • Granulocytes / metabolism*
  • Granulocytes / physiology
  • Humans
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / physiology
  • Models, Biological
  • Nitric Oxide / biosynthesis
  • Phagocytosis / drug effects
  • Phagocytosis / physiology
  • Phosphatidylinositol 3-Kinases / metabolism
  • Reactive Oxygen Species / metabolism
  • Second Messenger Systems / physiology*
  • Signal Transduction


  • Cytokines
  • Reactive Oxygen Species
  • Cyclic ADP-Ribose
  • Nitric Oxide
  • Abscisic Acid
  • Phosphatidylinositol 3-Kinases