Extracellular nucleotide and nucleoside signaling in vascular and blood disease

TY - JOUR

T1 - Extracellular nucleotide and nucleoside signaling in vascular and blood disease

AU - Idzko, Marco

AU - Ferrari, Davide

AU - Riegel, Ann-Kathrin

AU - Eltzschig, Holger K

N1 - © 2014 by The American Society of Hematology.

PY - 2014/8/14

Y1 - 2014/8/14

N2 - Nucleotides and nucleosides-such as adenosine triphosphate (ATP) and adenosine-are famous for their intracellular roles as building blocks for the genetic code or cellular energy currencies. In contrast, their function in the extracellular space is different. Here, they are primarily known as signaling molecules via activation of purinergic receptors, classified as P1 receptors for adenosine or P2 receptors for ATP. Because extracellular ATP is rapidly converted to adenosine by ectonucleotidase, nucleotide-phosphohydrolysis is important for controlling the balance between P2 and P1 signaling. Gene-targeted mice for P1, P2 receptors, or ectonucleotidase exhibit only very mild phenotypic manifestations at baseline. However, they demonstrate alterations in disease susceptibilities when exposed to a variety of vascular or blood diseases. Examples of phenotypic manifestations include vascular barrier dysfunction, graft-vs-host disease, platelet activation, ischemia, and reperfusion injury or sickle cell disease. Many of these studies highlight that purinergic signaling events can be targeted therapeutically.

AB - Nucleotides and nucleosides-such as adenosine triphosphate (ATP) and adenosine-are famous for their intracellular roles as building blocks for the genetic code or cellular energy currencies. In contrast, their function in the extracellular space is different. Here, they are primarily known as signaling molecules via activation of purinergic receptors, classified as P1 receptors for adenosine or P2 receptors for ATP. Because extracellular ATP is rapidly converted to adenosine by ectonucleotidase, nucleotide-phosphohydrolysis is important for controlling the balance between P2 and P1 signaling. Gene-targeted mice for P1, P2 receptors, or ectonucleotidase exhibit only very mild phenotypic manifestations at baseline. However, they demonstrate alterations in disease susceptibilities when exposed to a variety of vascular or blood diseases. Examples of phenotypic manifestations include vascular barrier dysfunction, graft-vs-host disease, platelet activation, ischemia, and reperfusion injury or sickle cell disease. Many of these studies highlight that purinergic signaling events can be targeted therapeutically.

KW - Adenosine

KW - Adenosine Triphosphate

KW - Extracellular Space

KW - Hematologic Diseases

KW - Humans

KW - Models, Biological

KW - Receptors, Purinergic P1

KW - Receptors, Purinergic P2

KW - Signal Transduction

KW - Vascular Diseases

KW - Journal Article

KW - Research Support, N.I.H., Extramural

KW - Research Support, Non-U.S. Gov't

KW - Review

U2 - 10.1182/blood-2013-09-402560

DO - 10.1182/blood-2013-09-402560

M3 - SCORING: Review article

C2 - 25001468

VL - 124

SP - 1029

EP - 1037

JO - BLOOD

JF - BLOOD

SN - 0006-4971

IS - 7

ER -