Alveolar Epithelial A2B @entity859 Receptors in Pulmonary Protection during Acute XXXX .

@entity1 @entity859 @entity24980 @entity3126 @entity55 @entity19 @entity23925 @entity651 @entity30562 @entity7112 @entity647
@entity647 ( @entity647 ) is an acute @entity55 that causes morbidity and mortality in critically ill @entity1 . However, there are many instances where @entity647 resolves spontaneously through endogenous pathways that help to control @entity55 . Previous studies have implicated the extracellular signaling molecule @entity859 and signaling events through the A2B @entity859 receptor in lung protection. In this context, we hypothesized that tissue-specific expression of the A2B @entity859 receptor is responsible for the previously described attenuation of @entity647 . To address this hypothesis, we exposed @entity19 with tissue-specific deletion of @entity23925 to @entity647 , utilizing a two-hit model where intratracheal LPS treatment is followed by injurious mechanical ventilation. Interestingly, a head-to-head comparison of @entity19 with deletion of @entity23925 in the myeloid lineage ( @entity23925 (loxP/loxP) @entity30562 Cre(+)), endothelial cells ( @entity23925 (loxP/loxP) @entity7112 Cre(+)), or alveolar epithelial cells ( @entity23925 (loxP/loxP) SPC Cre(+)) revealed a selective increase in disease susceptibility in @entity23925 (loxP/loxP) SPC Cre(+) @entity19 . More detailed analysis of @entity23925 (loxP/loxP) SPC Cre(+) @entity19 confirmed @entity55 and attenuated alveolar fluid clearance. To directly deliver an A2B @entity859 receptor-specific agonist to alveolar epithelial cells, we subsequently performed studies with inhaled @entity24980 . Indeed, aerosolized @entity24980 treatment was associated with @entity3126 , improved histologic @entity651 , and dampened @entity55 . Collectively, these findings suggest that alveolar epithelial A2B @entity859 receptor signaling contributes to lung protection, and they implicate inhaled A2B @entity859 receptor agonists in @entity647 treatment.
