Adenosine and ATPγS protect against bacterial pneumonia-induced acute lung injury

Autor:	Anita Kovacs-Kasa, Mary Cherian-Shaw, Christine Gross, Alexander D. Verin, Mary L Meadows, David J. Fulton
Jazyk:	angličtina
Rok vydání:	2020
Předmět:	0301 basic medicine Male Adenosine Lipopolysaccharide Vasodilator Agents Phosphatase Acute Lung Injury lcsh:Medicine Gene delivery Lung injury Pharmacology Article 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Adenosine Triphosphate Extracellular medicine Escherichia coli Pneumonia Bacterial Animals Phosphorylation Purine metabolism lcsh:Science Multidisciplinary Chronic obstructive pulmonary disease lcsh:R Affinity Labels respiratory system Mice Inbred C57BL 030104 developmental biology 030228 respiratory system chemistry lcsh:Q Bacterial outer membrane medicine.drug
Zdroj:	Scientific Reports, Vol 10, Iss 1, Pp 1-10 (2020) Scientific Reports
ISSN:	2045-2322
DOI:	10.1038/s41598-020-75224-0
Popis:	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′-(γ-thio)-triphosphate (ATPγS) added intravenously (i.v.). After 24 h of E. coli treatment, we found that injections of either adenosine or ATPγS 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 ATPγS increased oxygen saturation and reduced histopathological signs of lung injury in mice exposed to E. coli. Lastly, lung-targeting gene delivery of adenosine or ATPγS downstream effector, myosin phosphatase, significantly attenuated the E. coli-induced compromise of lung function. Collectively, our study has demonstrated that adenosine or ATPγS mitigates E. coli-induced ALI in mice and may be useful as an adjuvant therapy in future pre-clinical studies.
Databáze:	OpenAIRE
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