title: The role of purinergic signaling on deformation induced injury and repair responses of alveolar epithelial cells.
abstract: Cell wounding is an important driver of the innate immune response of ventilator-injured lungs. We had previously shown that the majority of wounded alveolus resident cells repair and survive deformation induced insults. This is important insofar as wounded and repaired cells may contribute to injurious deformation responses commonly referred to as biotrauma. The central hypothesis of this communication states that extracellular adenosine-5' triphosphate (ATP) promotes the repair of wounded alveolus resident cells by a P2Y2-Receptor dependent mechanism. Using primary type 1 alveolar epithelial rat cell models subjected to micropuncture injury and/or deforming stress we show that 1) stretch causes a dose dependent increase in cell injury and ATP media concentrations; 2) enzymatic depletion of extracellular ATP reduces the probability of stretch induced wound repair; 3) enriching extracellular ATP concentrations facilitates wound repair; 4) purinergic effects on cell repair are mediated by ATP and not by one of its metabolites; and 5) ATP mediated cell salvage depends at least in part on P2Y2-R activation. While rescuing cells from wounding induced death may seem appealing, it is possible that survivors of membrane wounding become governors of a sustained pro-inflammatory state and thereby perpetuate and worsen organ function in the early stages of lung injury syndromes. Means to uncouple P2Y2-R mediated cytoprotection from P2Y2-R mediated inflammation and to test the preclinical efficacy of such an undertaking deserve to be explored.
authors.affiliation: Thoracic Diseases Research Unit, Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, Minnesota, United States of America.
authors.forename: Hewan A
authors.initials: HA
authors.lastname: Belete
authors.forename: Rolf D
authors.initials: RD
authors.lastname: Hubmayr
authors.forename: Shaohua
authors.initials: S
authors.lastname: Wang
authors.forename: Raman-Deep
authors.initials: RD
authors.lastname: Singh
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D004847:Epithelial Cells / Q000276:immunology*; D007113:Immunity, Innate; D007249:Inflammation; D011650:Pulmonary Alveoli / Q000473:pathology*; D051381:Rats; D058473:Receptors, Purinergic P2Y2 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*; D014945:Wound Healing / Q000276:immunology*
chemical_list: D058473:Receptors, Purinergic P2Y2; D000255:Adenosine Triphosphate
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