GLUTATHIONE S-TRANSFERASES IN TRACHEOBRONCHIAL EPITHELIUM

The purpose of this study is to characterize glutathione S-transferase (GST) gene expression in airway epithelium both in vivo and in vitro. Immunohistochemical staining of nonhuman primate lungs of well-contro lled healthy animals reveals the presence of alpha- and pi-class GST i soenzymes in ciliated bronchial epithelium. The stain of mu-GST antibo dy is either very low or absent in some of these monkey lungs. We obse rved that primary tracheobronchial epithelial (TEE) cells isolated fro m human and monkey pulmonary tissues maintain a relatively high level of GST enzymatic activity in culture, compared with various immortaliz ed human TEE cell lines and other nonpulmonary cell lines. Northern bl ot analysis demonstrated the presence of mu-, pi-, and microsomal-GST messages but not the oc-class message in cultures of primary TEE cells as well as in various human TEE cell lines. The expression of mu- and pi-class GST genes can be further regulated in culture by various env ironmental factors; however, most of these regulating factors are asso ciated with TEE cell differentiation in culture. For instance, vitamin A treatment, which was shown to enhance mucous cell differentiation i n vitro, stimulated the message levels of mu- and pi-class GST. Furthe rmore, plating cells on collagen gel substrata, which also enhanced mu cous cell differentiation in culture, instead of plastic culture surfa ce, enhanced total GST enzymatic activity by eightfold, and this enhan cement is related to an increase in the expression of the pi-class GST gene. These results demonstrated that GST genes are differentially ex pressed and regulated by various environmental factors in primary TEE cells and various cell lines, and the regulation is correlated to the mucous cell differentiation in culture.