The role of ATP and purinergic-receptor-signalling in the pathogenesis of ALI/ARDS

Background: Extracellular ATP serves as a danger signal to alert the immune system after tissue damage by acting on P2X or P2Y receptors. Acute lung injury (ALI)/acute respiratory syndrome (ARDS) is characterized by rapid alveolar injury, inflammation, cytokine production, neutrophils accumulation and vascular leakage leading to lung oedema. While recent data point out to an important role of ATP/P2R-axis in chronic inflammatory lung diseases such as asthma and COPD, its role in ALI/ARDS is unknown.

Aims: To investigate the role of ATP and purinergic-receptor-signalling in the pathogenesis of ALI/ARDS.

Methods and Results: To address this hypothesis, we used a murine model of LPS induced ALI/ARDS. These studies revealed that intrapulmonary application of the ATP/ADP hydrolyzing enzyme apyrase or specific/unspecific P2R-Antagonists prior (prophylactic) or 24 hours after (therapeutic) LPS instillation decreased neutrophil trafficking into the lungs, as well as the levels of pro-inflammatory cytokines in bronchoalveolar fluid.

Conclusion: In summary we demonstrated, for the first time, that endogenous ATP contributes to the pathophysiology of LPS induced acute lung injury via activation of P2R. Thus targeting the ATP/P2R-axis might be a new promising option for the treatment of ALI/ARDS.

Key words: acute lung inflammation, apyrase/P2R-antagonists, ATP, BAL, cytokines