| Airway Epithelial Cell Responses to Ozone Injury George D. Leikauf1, Leigh G. Simpson1, Jeffrey Santrock2, Qiyu Zhao1, Joan Abbinante-Nissen1, Shaoying Zhou1, and Kevin E. Driscoll3 1Pulmonary Cell Biology Laboratory, Departments of Environmental Health, Molecular and Cellular Physiology, and Medicine, University of Cincinnati Medical Center, Cincinnati, Ohio;
2Biomedical Science Department, General Motors Research and Environmental Staff, Warren, Michigan;
3Health and Safety Division, Procter & Gamble Company, Miami Valley Laboratories, Cincinnati, Ohio Abstract
The airway epithelial cell is an important target in ozone injury. Once activated, the airway epithelium responds in three phases. The initial, or immediate phase, involves activation of constitutive cells, often through direct covalent interactions including the formation of secondary ozonolysis products--hydroxyhydroperoxides, aldehydes, and hydrogen peroxide. Recently, we found hydroxyhydroperoxides to be potent agonists of bioactive eicosanoid formation by human airway epithelial cells in culture. Other probable immediate events include activation and inactivation of enzymes present on the epithelial surface (e.g., neutral endopeptidase) . During the next 2 to 24 hr, or early phase, epithelial cells respond by synthesis and release of chemotactic factors, including chemokines--macrophage inflammatory protein-2, RANTES, and interleukin-8. Infiltrating leukocytes during this period also release elastase, an important agonist of epithelial cell mucus secretion and additional chemokine formation. The third (late) phase of ozone injury is characterized by eosinophil or monocyte infiltration. Cytokine expression leads to alteration of structural protein synthesis, with increases in fibronectin evident by in situ hybridization. Synthesis of epithelial antiproteases, e.g., secretory leukocyte protease inhibitor, may also increase locally 24 to 48 hr after elastase concentrations become excessive. Thus, the epithelium is not merely a passive barrier to ozone injury but has a dynamic role in directing the migration, activating, and then counteracting inflammatory cells. Through these complex interactions, epithelial cells can be viewed as the initiators (alpha) and the receptors (omega) of ozone-induced airway disease. -- Environ Health Perspect 103 (Suppl 2) :91-95 (1995) Key words: air pollution, asthma, bronchitis, cytokines, inflammation, eicosanoids, aldehydes, hydroxyhydroperoxides, hydrogen peroxide
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