Airway epithelial cell responses to ozone injury.

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., secretary 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)

Interaction with Epithelial Cells Modifies Airway Macrophage Response to Ozone

“…The airway epithelium acts as both a physical barrier against the inhaled environment and orchestrator of the innate immune response (10). Acute O 3 exposure damages epithelial cells, leading to increased airway permeability, cell death, and the release of cytokines/chemokines and danger signals that can activate local immune cells, such as Macs (1,11,12). Airway Macs reside along the airway epithelium and act as key members of the innate immune system by clearing pathogens and debris via phagocytosis, and releasing cytokines and chemokines to regulate the inflammatory response (9,13).…”

“…In addition, the lung microenvironment has been shown to influence Mac phenotype and function (16). However, most in vitro studies investigating the cellular inflammatory response to O 3 have used monoculture systems, which do not address the interaction between multiple cell types in the airway, and have limited applicability to in vivo situations (11,12,(17)(18)(19)(20) (22,23). Equal volumes of media were added to the apical side of epithelial cell monocultures.…”

Detection of Aldehydes in Bronchoalveolar Lavage of Rats Exposed to Ozone

“…Third, we have detected significant increases in the amounts of aliphatic alde- hydes in the bronchoalveolar lavage of rats following ozone exposure (Cueto et al, , 1994. Finally, oxidized lipids are known to act as messengers of a variety of cellular signals, including the inflammatory response (Pryor et al, 1995b;Wright et al, 1994b;Leikauf et al, 1993Leikauf et al, , 1995Stremler et al, 1989;Zimmerman et al, 1995).…”

“…The initial ozonation products are known to include molecules formed from the ozonation of lipids (Goldstein and Balchum, 1967;Goldstein etal, 1969;Balchum etal., 1971;Mudd and Freeman, 1977;Pryor et al, 1976;Leikauf et al, 1993). These primary reaction products then relay the effects of ozone to deeper tissue strata (Pryor, 1993;Goldstein and Balchum, 1967;Pryor et al, 1995b;Leikauf et al, 1995;Wright etal., 1994b).…”

NADPH:Quinone Oxidoreductase 1 Regulates Host Susceptibility to Ozone via Isoprostane Generation

“…Ozone inhalation causes several pulmonary responses including increased cough, chest pain, decreased forced expiratory volume in 1 s, airway hyperreactivity (4), and increased airway inflammation, specifically neutrophilic inflammation (1,5). Ozone triggers these physiologic sequelae via the generation of reactive oxygen species that act as potent intracellular signals.…”