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


CONCLUSIONS
Our observations suggest that the ATP-P2Y receptor system is partially involved in the pathogenesis of ventilator-induced lung injury.
Matsuyama
Hiroki
H
Department of Anesthesiology and Intensive Care, Kyoto Prefectural University of Medicine, Kyoto, Japan. matuyama@koto.kpu-m.ac.jp
Amaya
Fumimasa
F
Hashimoto
Soshi
S
Ueno
Hiroshi
H
Beppu
Satoru
S
Mizuta
Mitsuhiko
M
Shime
Nobuaki
N
Ishizaka
Akitoshi
A
Hashimoto
Satoru
S
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D008297:Male; D051379:Mice; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D015398:Signal Transduction; D055397:Ventilator-Induced Lung Injury / Q000378:metabolism*
D018048:Receptors, Purinergic P2; D000255:Adenosine Triphosphate