Of the environmental photoxidant pollutants, ozone is of particular importance because of its predominance in photochemical smog and its remarkable reactivity. The effects of ozone on airway secretion have only been partially characterized. The purpose of this proposal is to study the effects of ozone on submucosal glandular secretion of the trachea. Two important basic questions will be addressed: 1) what is the effect; and 2) what is the mechanism of this effect. Our hypothesis is that alterations in glandular secretion occur as a result of either: a) sensitization of irritant receptors of airways and increased reflex secretion from submucosal glands, and/or b) recruitment of inflammatory cells into the trachea and release of mediators by these cells which indirectly alters glandular secretion. Two experimental models will be employed: 1) explants of tracheal submucosal glands of ferrets; and 2) tantalum coated surface of pig trachea, in vivo (hillock experiments). Ferrets or pigs will undergo either acute, short-term, or long-term exposure to ozone in various concentrations. Initial studies with explants will characterize the effects of these exposures on baseline glycoconjugate secretion and the dose-related responses of secretion to known secretogogues. Subsequent experiments utilizing various anti-inflammatory agents will employ explants to determine if the ozone-induced alterations in glyconjugate secretion can be aborted by pre-treatment with these agents. Initial studies with tantalum-coated pig trachea, in vivo, will quantitate the effects of ozone exposure on the volume of secretion from individual gland ducts under baseline conditions and following stimulation with either a non-specific irritant or with known secretogogues. If the ozone exposure results in an augmented secretory response in vivo to the non-specific irritant, then studies will be performed to determine if this response is related to a vagally mediated reflex and to ascertain if the response remains despite the use of anti-inflammatory agents. The study of the alteration in normal secretory function which may occur with oxidant injury will provide an opportunity to learn more about the pathophysiology of airway secretion.
| McBride, R K; Stone, K K; Marin, M G (1993) Oxidant injury alters barrier function of ferret tracheal epithelium. Am J Physiol 264:L165-74 |
| McBride, R K; Stone, K K; Marin, M G (1992) Arachidonic acid increases cholinergic secretory responsiveness of ferret tracheal glands. Am J Physiol 262:L694-8 |
| McBride, R K; Oberdoerster, G; Marin, M G (1991) Effects of ozone on the cholinergic secretory responsiveness of ferret tracheal glands. Environ Res 55:79-90 |
| Culp, D J; McBride, R K; Graham, L A et al. (1990) Alpha-adrenergic regulation of secretion by tracheal glands. Am J Physiol 259:L198-205 |
