RGD Reference Report - Adenosine receptor A1 regulates polymorphonuclear cell trafficking and microvascular permeability in lipopolysaccharide-induced lung injury. - Rat Genome Database

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Adenosine receptor A1 regulates polymorphonuclear cell trafficking and microvascular permeability in lipopolysaccharide-induced lung injury.

Authors: Ngamsri, KC  Wagner, R  Vollmer, I  Stark, S  Reutershan, J 
Citation: Ngamsri KC, etal., J Immunol. 2010 Oct 1;185(7):4374-84. Epub 2010 Aug 20.
RGD ID: 5129093
Pubmed: PMID:20729330   (View Abstract at PubMed)
DOI: DOI:10.4049/jimmunol.1000433   (Journal Full-text)

Extracellular adenosine and adenosine receptors are critically involved in various inflammatory pathways. Adenosine receptor A1 (A1AR) has been implicated in mediating transmigration of leukocytes to sites of inflammation. This study was designed to characterize the role of A1AR in a murine model of LPS-induced lung injury. LPS-induced transmigration of polymorphonuclear cells (PMNs) and microvascular permeability was elevated in A1AR(-/-) mice. Pretreatment of wild-type mice with the specific A1AR agonist 2'Me-2-chloro-N6-cyclopentyladenosine attenuated PMN accumulation in the interstitium and alveolar space as well as microvascular permeability. Lower PMN counts in the lungs of pretreated wild-type mice were associated with reduced amounts of the chemotactic cytokines TNF-alpha, IL-6, and CXCL2/3 in the bronchoalveolar lavage. Pretreatment was only effective when A1AR was expressed on hematopoietic cells as demonstrated in chimeric mice. These findings were confirmed by in vitro transmigration assays demonstrating that chemokine-induced transmigration of PMNs was reduced when PMNs but not when pulmonary endothelial or alveolar epithelial cells were pretreated. 2'Me-2-chloro-N6-cyclopentyladenosine prevented pulmonary endothelial but not epithelial cells from LPS-induced cellular remodeling and cell retraction. Our data reveal what we believe to be a previously unrecognized distinct role of A1AR for PMN trafficking and endothelial integrity in a model of acute lung injury.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
lung disease  ISOAdora1 (Mus musculus)5129093; 5129093Acute Lung InjuryRGD 
lung disease  IMP 5129093Acute Lung InjuryRGD 

Objects Annotated

Genes (Rattus norvegicus)
Adora1  (adenosine A1 receptor)

Genes (Mus musculus)
Adora1  (adenosine A1 receptor)

Genes (Homo sapiens)
ADORA1  (adenosine A1 receptor)


Additional Information