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

The airway epithelial lining serves as an efficient barrier against penetra tion of exogenous particles and macromolecules. Disruption of this barrier following O-3 exposure represents a state of compromised epithelial defense s leading to increased transmucosal permeability. Although the barrier disr uption following an acute exposure is transient in nature, the brief period of disruption caused by O-3, an oxidant air pollutant, provides an opportu nity for facilitated entry of a potentially toxic particulate copollutant(s ) across the airway epithelia. The subsequent deposition and retention of t he copollutant(s) in the subepithelial compartment for prolonged periods ad ds the risk of injury due to chronic exposure following an acute episode. T oxicological studies from several laboratories have demonstrated alteration s in epithelial permeability, suggestive of barrier disruption, in animals and humans exposed to O-3. inflammatory cells represent another important c omponent of pulmonary defenses, but upon activation these cells can both in duce and sustain injury. The recruitment of these cells into the lung follo wing O-3 exposure presents a risk of tissue damage through the release of t oxic mediators by activated inflammatory cells. Several studies have report ed 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 le ukocytes in the bronchoalveolar lavage (BAL) or in lung parenchyma, was acc ompanied by either an increased tracer transport across the airway mucosa o r an elevation in the levels of total protein and/or albumin in the BAL. Th e magnitude of response and the time at which the permeability changes and inflammatory response peaked varied with O-3 concentration, exposure durati on, and the mode of analysis. The responsiveness to O-3 also appeared to va ry with the animal species, and increased under certain conditions such as physical activity and pregnancy. Some of the effects seen after an acute ex posure to O-3 were modified upon repeated exposures. The responses followin g repeated exposures included attenuation, persistence, or elevation of per meability and inflammation. Mechanistic studies implicate chemotactic facto rs, cellular mediators, and cell-surface-associated molecules in the induct ion of inflammation and lung injury. in discussing these studies, this revi ew 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.