RGD Reference Report - Therapeutic anti-inflammatory effects of myeloid cell adenosine receptor A2a stimulation in lipopolysaccharide-induced lung injury. - Rat Genome Database

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Therapeutic anti-inflammatory effects of myeloid cell adenosine receptor A2a stimulation in lipopolysaccharide-induced lung injury.

Authors: Reutershan, J  Cagnina, RE  Chang, D  Linden, J  Ley, K 
Citation: Reutershan J, etal., J Immunol. 2007 Jul 15;179(2):1254-63.
RGD ID: 4890370
Pubmed: PMID:17617618   (View Abstract at PubMed)

To determine the role of the adenosine receptor A2a in a murine model of LPS-induced lung injury, migration of polymorphonuclear leukocytes (PMNs) into the different compartments of the lung was determined by flow cytometry, microvascular permeability was assessed by the extravasation of Evans blue, and the release of chemotactic cytokines into the alveolar airspace was determined by ELISA. Measurements were performed in wild-type and A2a gene-deficient mice (A2a(-/-)). To differentiate the role of A2a on hemopoietic and nonhemopoietic cells, we created chimeric mice by transfer of bone marrow (BM) between wild-type and A2a(-/-) mice and used mice that lacked A2a expression selectively on myeloid cells (A2a(flox/flox) x LysM-cre). A specific A2a receptor agonist (ATL202) was used to evaluate its potential to reduce lung injury in vivo. In wild-type mice, therapeutic treatment with ATL202 reduced LPS-induced PMN recruitment, and release of cytokines. Pretreatment, but not posttreatment, also reduced Evans blue extravasation. In the BM chimeric mice lacking A2a on BM-derived cells, PMN migration into the alveolar space was increased by approximately 50%. These findings were confirmed in A2a(flox/flox) x LysM-cre mice. ATL202 was only effective when A2a was present on BM-derived cells. A2a agonists may be effective at curbing inflammatory lung tissue damage.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
lung disease  ISOAdora2a (Mus musculus)4890370; 4890370Acute Lung InjuryRGD 
lung disease  IDA 4890370Acute Lung InjuryRGD 

Objects Annotated

Genes (Rattus norvegicus)
Adora2a  (adenosine A2a receptor)

Genes (Mus musculus)
Adora2a  (adenosine A2a receptor)

Genes (Homo sapiens)
ADORA2A  (adenosine A2a receptor)


Additional Information