Hypocapnic Alkalosis Enhances Oxidant-induced Apoptosis of Human Alveolar Epithelial Type II Cells

Abstract

Apoptosis of alveolar epithelial type II (AEC-II) cells induced by reactive oxygen species (ROS) contributes to extensive alveolar damage during acute lung injury. Hypercapnic acidosis and hypocapnic alkalosis are known to modulate ROSmediated lung damage. This study assessed the effects of acid–base balance disturbances on hydrogen peroxide (H₂O₂)-induced apoptosis of the AEC-II-like human cell line A549, which was cultured under different conditions of pH and CO₂ tension (normal pH and CO₂, hypercapnic acidosis, metabolic acidosis, hypocapnic alkalosis and metabolic alkalosis). H₂O₂-induced apoptosis was assessed by a dye-uptake bioassay and induction of caspase activity, which were quantified using analytical digital photomicroscopy. Acidosis or alkalosis of the culture medium alone did not induce A549 cell apoptosis. Hypocapnic alkalosis significantly increased H₂O₂-induced apoptosis and caspase activation of A549 cells. Metabolic alkalosis non-significantly increased H₂O₂-induced A549 cell apoptosis and caspase activation. These data suggest that hypocapnic alkalosis intensifies oxidative-induced apoptosis of alveolar epithelial cells.