EFFECTS OF 03/ENDOTOXIN COEXPOSURE ON NASAL EPITHELIUM

Michigan State University, East Lansing MI

Investigators

Abstract

Exposure of people to more that one air pollutant is common, but there is little understanding of the risk to human health of coexposure relative to that presented by a single pollutant. The goal of this project is to understand how the inflammation induced by inhalation of bacterial endotoxin affects the response of nasal airway epithelium to ozone, the principal oxidant air pollutant in photochemical smog. Ozone exposure causes inflammation that is followed by mucous cell metaplasia (MCM) which is the appearance of mucous secreting cells in regions of nasal epithelium normally devoid of secretory cells. We have recently reported that endotoxin significantly potentiates the development and magnitude of ozone-induced MCM, and that this response is dependent on the presence of neutrophils. Specific aims in this proposal test the hypothesis that neutrophils or their secreted products mediate endotoxin-induced potentiation of MCM caused by exposure to ozone. Studies will first evaluate the effects of neutrophil degranulation products on epithelial cell changes after exposure to ozone in (1) upper airways of neutrophil-depleted rats and in (2) a novel in vitro system of cultured nasal tissue explants. Studies will next address the role of neutrophil proteases as the primary neutrophil product that mediates the ability of endotoxin to potentiate ozone- induced MCM. Morphometric, histochemical, immunochemical, and molecular techniques will be used to identify temporal alterations in epithelial cell populations, intraepithelial mucosubstances, mucin gene expression, and the appearance of cytokines in culture medium and tissues. These results will help define the mechanisms involved in the interaction of a biogenic agent (ie,endotoxin) and ozone, and illustrate the potential consequences of this coexposure to human health.