Role of pulmonary adenosine during hypoxia: extracellular generation, signaling and metabolism by surface adenosine deaminase/CD26.

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Van Linden A, Eltzschig HK

Role of pulmonary adenosine during hypoxia: extracellular generation, signaling and metabolism by surface adenosine deaminase/CD26.

Expert Opin Biol Ther. 2007 Sep;7(9):1437-47.

PubMed ID

17727332 [ View in PubMed

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Abstract

Numerous parallels exist between limited oxygen availability (hypoxia) and acute inflammation. The lungs in particular are prone to acute inflammation during hypoxia, resulting in pulmonary edema, vascular leakage and neutrophil infiltration. The innate response elicited by hypoxia is associated with increased extracellular adenosine effects. Although studies on acute pulmonary hypoxia show a protective role of extracellular adenosine by attenuating pulmonary edema and excessive inflammation, chronic elevation of pulmonary adenosine may be detrimental. Adenosine deaminase (ADA)-deficient mice, for example, develop signs of chronic pulmonary injury in association with highly elevated levels of adenosine. Thus, the authors hypothesized the existence of hypoxia-elicited clearance mechanisms to offset deleterious influences of chronically elevated adenosine. Such studies indicated a second response to hypoxia characterized by pulmonary induction of ADA and CD26. In fact, hypoxia-inducible ADA is enzymatically active and tethered on the outside of the membrane via CD26 to form a complex capable of degrading extracellular adenosine to inosine. This paper reviews metabolic and transcriptional changes of extracellular adenosine generation, signaling and degradation during acute and prolonged pulmonary hypoxia.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Pegademase	Adenosine	Small molecule	Humans	Yes	Metabolizer	Details