Adenosine and ATP?S protect against bacterial pneumonia-induced acute lung injury.

ABSTRACT: Lipopolysaccharide (LPS), a component of the outer membrane of gram-negative bacteria, disrupts the alveolar-capillary barrier, triggering pulmonary vascular leak thus inducing acute lung injury (ALI). Extracellular purines, adenosine and ATP, protected against ALI induced by purified LPS. In this study, we investigated whether these purines can impact vascular injury in more clinically-relevant E.coli (non-sterile LPS) murine ALI model. Mice were inoculated with live E. coli intratracheally (i.t.) with or without adenosine or a non-hydrolyzable ATP analog, adenosine 5'-(?-thio)-triphosphate (ATP?S) added intravenously (i.v.). After 24 h of E. coli treatment, we found that injections of either adenosine or ATP?S 15 min prior or adenosine 3 h after E.coli insult significantly attenuated the E.coli-mediated increase in inflammatory responses. Furthermore, adenosine prevented weight loss, tachycardia, and compromised lung function in E. coli-exposed mice. Accordingly, treatment with adenosine or ATP?S increased oxygen saturation and reduced histopathological signs of lung injury in mice exposed to E. coli. Lastly, lung-targeting gene delivery of adenosine or ATP?S downstream effector, myosin phosphatase, significantly attenuated the E. coli-induced compromise of lung function. Collectively, our study has demonstrated that adenosine or ATP?S mitigates E. coli-induced ALI in mice and may be useful as an adjuvant therapy in future pre-clinical studies.

SUBMITTER: Gross CM 

PROVIDER: S-EPMC7581771 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature