Cell wounding and repair are important drivers of the innate immune response of ventilator‐injured lungs. Cells repair plasma membrane (PM) wounds by several mechanisms including non‐secretory exocytosis and it is therefore not surprising that extra‐cellular ATP, a secretagogue, enhances PM repair. Neither the responsible purinergic receptor sub‐type nor the downstream signaling pathways have been identified.Expression of P2Y2R in A549 cells was validated by immunocytochemistry and immunoblot experiments using anti‐P2Y2R (Chemicon). Confluent A549 cells were incubated with the P2Y2 antagonist Suramin (400μM), ATP (50ìM) or ATP hydrolase Apyrase (20U/ml) and stretched by 30% at 8 cycles/min for 5 min. 2 min later, the cells were labeled with Propidium Iodide (PI; 4μl/ml), trypsinized and subjected to flow cytometry. PI + cells were considered wounded and necrotic. Pretreatment of A549 cells with Suramin showed a significantly higher fraction of PI + cells compared to controls (47 ± 9 % vs 22 ± 5%, p<0.05), while the addition of extracellular ATP appeared to promote PM wound repair (6± 1%, p<0.01). In contrast, pretreatment with apyrase did not significantly alter the number of necrotic cells (26 ± 6%)Our results suggest that ATP promotes PM wound repair by a P2Y2R dependent mechanism. The Apyrase data raises the possibility that ATP metabolites may also modulate PM repair.Support HL63178