Ozone-induced lung inflammation and mucosal barrier disruption: Toxicology, mechanisms, and implications

The airway epithelial lining serves as an efficient barrier against penetration of exogenous particles and macromolecules. Disruption of this barrier following O-3 exposure represents a state of compromised epithelial defenses leading to increased transmucosal permeability. Although the barrier disruption following an acute exposure is transient in nature, the brief period of disruption caused by O-3, an oxidant air pollutant, provides an opportunity for facilitated entry of a potentially toxic particulate copollutant(s) across the airway epithelia. The subsequent deposition and retention of the copollutant(s) in the subepithelial compartment for prolonged periods adds the risk of injury due to chronic exposure following an acute episode. Toxicological studies from several laboratories have demonstrated alterations in epithelial permeability, suggestive of barrier disruption, in animals and humans exposed to O-3. inflammatory cells represent another important component of pulmonary defenses, but upon activation these cells can both induce and sustain injury. The recruitment of these cells into the lung following O-3 exposure presents a risk of tissue damage through the release of toxic mediators by activated inflammatory cells. Several studies have reported concomitant changes in permeability and recruitment of the inflammatory cells in the lung following O-3 exposure. In these studies, an inflammatory response, as detected by an increase in the number of polymorphonuclear leukocytes in the bronchoalveolar lavage (BAL) or in lung parenchyma, was accompanied by either an increased tracer transport across the airway mucosa or an elevation in the levels of total protein and/or albumin in the BAL. The magnitude of response and the time at which the permeability changes and inflammatory response peaked varied with O-3 concentration, exposure duration, and the mode of analysis. The responsiveness to O-3 also appeared to vary with the animal species, and increased under certain conditions such as physical activity and pregnancy. Some of the effects seen after an acute exposure to O-3 were modified upon repeated exposures. The responses following repeated exposures included attenuation, persistence, or elevation of permeability and inflammation. Mechanistic studies implicate chemotactic factors, cellular mediators, and cell-surface-associated molecules in the induction of inflammation and lung injury. in discussing these studies, this review serves to introduce the mucosal barrier functions in the lung, evaluates inflammatory and permeability consequences of O-3, addresses mechanisms of inflammatory reactions, and offers alternate viewpoints.