Abscisic acid is an endogenous cytokine in human granulocytes with cyclic ADP-ribose as second messenger.
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.
Bruzzone
Santina
S
Department of Experimental Medicine, Section of Biochemistry, University of Genova, Viale Benedetto XV/1, 16132 Genoa, Italy.
Moreschi
Iliana
I
Usai
Cesare
C
Guida
Lucrezia
L
Damonte
Gianluca
G
Salis
Annalisa
A
Scarfì
Sonia
S
Millo
Enrico
E
De Flora
Antonio
A
Zocchi
Elena
E
D000040:Abscisic Acid / Q000378:metabolism* / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology; D036563:Cyclic ADP-Ribose / Q000032:analysis / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006098:Granulocytes / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology; D008954:Models, Biological; D009569:Nitric Oxide / Q000096:biosynthesis; D010587:Phagocytosis / Q000187:drug effects / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015290:Second Messenger Systems / Q000502:physiology*; D015398:Signal Transduction
D016207:Cytokines; D017382:Reactive Oxygen Species; D036563:Cyclic ADP-Ribose; D009569:Nitric Oxide; D000040:Abscisic Acid; D019869:Phosphatidylinositol 3-Kinases