Abstract

Carboxylesterases (CE) exhibit high activity in the nasal mucosae and produce acid metabolites toxic to the olfactory epithelium following exposures to inhaled esters. The regional distribution and activity of CE have been studied in rodents, but no comparative studies have examined regional localization or activity in dog or human nasal tissues. We determined the immunohistochemical distributions of CE in the nasal respiratory and olfactory mucosae of Beagle dogs, and the nasal respiratory mucosa of the human nose and compared these distributions to those in the F344 rat. In the dog respiratory mucosa, the greatest CE immunoreactivity was in the subepithelial glands and surface epithelial cells. In the olfactory mucosa, immunoreactivity was observed in the apical portion of the sustentacular cells, and in duct cells and acinar cells of Bowman's glands. This distribution is similar to that found in rat, except the subepithelial glands of the rat respiratory mucosa showed little to no immunoreactive CE. The human respiratory mucosa showed immunostaining in surface epithelial cells as well as glandular cells. Immunostaining in the human tissue samples was dramatically reduced in the presence of hyperplastic lesions and virtually eliminated in samples with squamous metaplasia. The data indicate that the distribution of CE is very similar in healthy nasal mucosae across the three species studied. However, the loss of CE immunoreactivity correlated with nasal epithelial lesions in the human samples suggests enzymatic activity may be compromised by insults to nasal tissues. Further studies of CE activity in animals following nasal insult could improve the ability to predict human responses to inhaled esters.

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