Lung epithelial cells release ATP during ozone exposure: signaling for cell survival.

The common air pollutant ozone causes acute toxicity to human airways. In primary and transformed epithelial cells from all levels of human or rat airways, ozone levels relevant to air pollution (50-200 ppb) increased extracellular [ATP] within 7-30 min. A human bronchial epithelial cell line (16HBE14o(-)) that forms electrically resistant polarized monolayers had up to 10-fold greater apical than basolateral surface extracellular [ATP] within 7 min of ozone exposure.

Interleukin-1 receptor antagonist attenuates airway hyperresponsiveness following exposure to ozone.

The role of an interleukin (IL)-1 receptor antagonist (IL-1Ra) on the development of airway hyperresponsiveness (AHR) and airway inflammation following acute O(3) exposure in mice was investigated. Exposure of C57/BL6 mice to O(3) at a concentration of 2.0 ppm or filtered air for 3 h resulted in increases in airway responsiveness to inhaled methacholine (MCh) 8 and 16 h after the exposure, and an increase in neutrophils in the bronchoalveolar lavage (BAL) fluid.

Hyperoxia-induced DNA damage causes decreased DNA methylation in human lung epithelial-like A549 cells.

The effect of hyperoxia on levels of DNA damage and global DNA methylation was examined in lung epithelial-like A549 cells. DNA damage was assessed by the single-cell gel electrophoresis (comet assay) and DNA methylation status by the cytosine extension assays. Cells exposed to ionizing radiation (0, 1, 2, 4, or 8 Gy) showed increasing rates of percentage of DNA in the tail and tail length with increasing radiation dose.

Complement activation is critical to airway hyperresponsiveness after acute ozone exposure.

Ozone (O3) can induce airway hyperresponsiveness (AHR) and neutrophilic inflammation. We evaluated the role of complement in development of AHR and inflammation after acute O3 exposure in mice. Mice were exposed to O3 at 2 ppm for 3 hours, and airway responsiveness to methacholine was measured 8 hours after O3 exposure.

An automated system for exposure of cultured cells and other materials to ozone.

Ozone, a highly reactive oxidant gas, is a major constituent of urban air pollution. Studies of the toxic effects of ozone on cultured cells and other materials are most appropriately conducted under conditions of humidity, temperature, and ozone concentration similar to those in which those materials are naturally exposed. An automated system designed for exposure of cultured cells and other materials to environmentally relevant levels of ozone under nearly physiological conditions is described.

Hypoxia protects human lung microvascular endothelial and epithelial-like cells against oxygen toxicity: role of phosphatidylinositol 3-kinase.

Hypoxic preconditioning is protective against oxidant-related damage in various organs, such as the heart. We previously showed that rats exposed to hypoxia also exhibit resistance to lethal pulmonary oxygen toxicity. The underlying mechanism and whether similar preconditioning is applicable to cellular models is unknown.

Elevated expression of hexokinase II protects human lung epithelial-like A549 cells against oxidative injury.

Increased glucose utilization and hexokinase (HK)-II expression are adaptive features of lung cells exposed to hypoxia or hyperoxia. HK-II is the most regulated isoform of HK. Whether its overexpression could be protective against oxidative stress was explored in human lung epithelial-like (A549) cells.

Oxidized phospholipids derived from ozone-treated lung surfactant extract reduce macrophage and epithelial cell viability.

Ozone is known to be a highly toxic gas present in the urban air which exerts its effect on pulmonary tissue through its facile chemical reactions with target molecules in the airway. One of the first barriers encountered by ozone is epithelial lining fluid which contains pulmonary surfactant rich in glycerophosphocholine lipids. The reaction of ozone with calf lung surfactant extract was found to result in the production of 1-palmitoyl-2-(9'-oxo-nonanoyl)-glycerophosphocholine (16:0a/9-al-GPCho) as an expected product of the ozonolysis of abundant unsaturated phospholipids containing unsaturated fatty acyl groups with a double bond at carbon-9.