Effects of ozone and endotoxin coexposure on rat airway epithelium: Potentiation of toxicant-induced alterations

Tropospheric ozone is the major oxidizing component in photochemical smog a nd is one of the most pervasive problems to human health of the criteria ai r pollutants for which the National Ambient Air Quality Standards have been designated by the Clean Air Act. Although many adverse health effects of o zone exposure have been documented in both humans and laboratory animals, c ontroversy surrounds the establishment and implementation of ozone standard s set forth by the U.S. Environmental Protection Agency. Because people are commonly exposed to more than one air pollutant at a time, studies that ex amine coexposures to airborne materials may be more relevant for assessing their risks to human health. Airborne biogenic substances such as pollens, spores, and bacterial products are ubiquitous in the environment, and when inhaled can cause adverse respiratory symptoms. One such biogenic agent, ba cterial endotoxin, is a potent stimulus of airway inflammation and is a ubi quitous airborne contaminant commonly found in domestic, agricultural, and industrial settings. Little is known about the interaction of exposures to biogenic substances and criteria air pollutants such as ozone. In the last few years we have performed a series of studies in rodents that examined th e biologic responses of the respiratory epithelium after airway exposures t o both endotoxin and ozone. When exposed to ozone (0.5 ppm 8 hr/day for 3 d ays), Fischer rats develop lesions in the nasal transitional epithelium, wh ereas intranasal instillation of endotoxin (20 mug) elicits epithelial lesi ons in the respiratory epithelium of the nose and conducting airways. Our s tudies were designed to examine how exposure to one toxicant may affect the airway epithelial lesions induced by the other toxicant. We investigated t he potential role of acute inflammation in the enhancement of airway epithe lial lesions after exposure of these two toxicants in neutrophil-sufficient and neutrophil-deficient rodents. A summary of these results indicates tha t epithelial and inflammatory responses to coexposure of these two pollutan ts are greater than those elicited by either agent alone. Interestingly, ea ch toxicant enhances the epithelial alterations induced by the other. Furth ermore, the synergistic effects elicited by coexposure to ozone and endotox in are mediated partly by neutrophils. These studies provided some new insi ghts into how inhaled co-pollutants interact to initiate and promote altera tions of airway epithelium. Further studies with these and other air pollut ants will help define their true risk to human health.