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Respiratory Research
Published in: Respiratory Research 1/2008

Open Access 01-12-2008 | Research

Acute lung inflammation and ventilator-induced lung injury caused by ATP via the P2Y receptors: an experimental study

Authors: Hiroki Matsuyama, Fumimasa Amaya, Soshi Hashimoto, Hiroshi Ueno, Satoru Beppu, Mitsuhiko Mizuta, Nobuaki Shime, Akitoshi Ishizaka, Satoru Hashimoto

Published in: Respiratory Research | Issue 1/2008

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Abstract

Background

Extracellular adenosine 5'-triphosphate (ATP) is an endogenous signaling molecule involved in multiple biological phenomena, including inflammation. The effects of extracellular ATP in the lung have not been fully clarified. This study examined 1) the biological roles of extracellular ATP in the pathogenesis of lung inflammation and 2) the possibility of involvement of extracellular ATP in mechanical ventilation-induced lung injury.

Methods

The effects of intratracheal ATP on lung permeability, edema or lung inflammation were assessed by measurements of the lung wet-to-dry weight ratio and lung permeability index, immunohistochemistry and expression of key cytokines by real-time polymerase chain reaction. The ATP concentration in broncho-alveolar lavage (BAL) fluid from mice mechanically ventilated was measured by luciferin-luciferase assay. The suppressive effects of a P2 receptor antagonist on ventilator-induced lung inflammation were also examined.

Results

ATP induced inflammatory reactions in the lung mainly via the ATP-P2Y receptor system. These reactions were alleviated by the co-administration of a specific P2 receptor antagonist. Mechanical ventilation with a large tidal volume caused lung inflammation and increased the ATP concentration in BAL fluid. P2 receptor antagonism partially mitigated the inflammatory effects of large tidal volume ventilation.

Conclusion

Our observations suggest that the ATP-P2Y receptor system is partially involved in the pathogenesis of ventilator-induced lung injury.
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Metadata
Title
Acute lung inflammation and ventilator-induced lung injury caused by ATP via the P2Y receptors: an experimental study
Authors
Hiroki Matsuyama
Fumimasa Amaya
Soshi Hashimoto
Hiroshi Ueno
Satoru Beppu
Mitsuhiko Mizuta
Nobuaki Shime
Akitoshi Ishizaka
Satoru Hashimoto
Publication date
01-12-2008
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2008
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/1465-9921-9-79

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