Extracellular ATP is a danger signal activating P2X7 Receptor in a LPS mediated inflammation (ARDS)

This study examined the role of extracellular ATP in recruiting inflammatory cells to the lung after induction of acute lung injury (ALI) with lipopolysaccharide (LPS). Extracellular ATP serves as a danger signal to alert the immune system of tissue damage by acting on P2X or P2Y receptors. However, the precise mechanism is poorly understood. Our objective was to investigate the functional role of P2X7 receptor in the pathogenesis of acute lung injury (ALI) in vivo. Here we show that inhalative LPS cause an acute accumulation of ATP in the airways of mice. Purinergic receptor antagonists have been used in both therapeutic and prophylactic models and leaded reduction in the ATP-Level and the total cell count in bronchoalveolar lavage (BALF). A succession of experiment with P2X7R-/- and WT chimera animals revealed that the hematopoetic system plays a pivatol role in the observed effect. Finally, we elucidated the contribution of different cell-type specific knockdown of P2X7 receptor, such as LysMCre (macrophages/neutrophils) P2X7fl, CCTCre P2X7fl (conducting airway epithelia), CD4Cre P2X7fl (lymphocytes), SPCTetoCre P2X7fl (airway-epithelial cells), in the pathogenesis of ALI. This decision of P2X7 Receptor may be a new therapeutic target for a treatment in acute lung injury (ALI). Key words: acute lung inflammation, P2X7, KN62, cell-type-specific knockdown of P2X7, BAL, ATP.