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(American Journal of Pathology. 2002;160:1991-2000.)
© 2002 American Society for Investigative Pathology

Regular Articles

Increased Localization and Substrate Activation of Protein Kinase C in Lung Epithelial Cells following Exposure to Asbestos

Karen M. Lounsbury^*, Maria Stern, Douglas Taatjes, Susan Jaken and Brooke T. Mossman

From the Departments of Pharmacology^*and Pathology,University of Vermont, Burlington, Vermont

The protein kinase C (PKC) family consists of several isozymes whose substrates may be necessary for the regulation of key cellular events important in the pathogenesis of proliferative diseases. Asbestos is a carcinogen and fibroproliferative agent in lung that may cause cell signaling events through activation of PKC. Here we used a murine inhalation model of asbestos-induced inflammation and fibrosis to examine immunoreactivity of PKC and its substrate, phosphorylated-adducin (p-adducin), in cells of the lung. Moreover, we characterized PKC and p-adducin expression in a pulmonary epithelial cell line (C10) in both log versus confluent cells and in cells after mechanical wounding or crocidolite asbestos exposure. Both PKC and p-adducin were almost exclusively expressed in bronchiolar and alveolar type II (ATII) epithelial cells in lung sections and increased in these cell types after inhalation of asbestos by mice. Increases in membrane and nuclear localization of PKC were seen in log phase as compared to confluent C10 cells. Moreover, enhanced immunoreactivity of PKC was observed in epithelial cells expressing proliferating cell nuclear antigen (PCNA) after mechanical wounding or exposure to asbestos fibers. These studies show that activated PKC in pulmonary epithelial cells is a consequence of inhalation of asbestos and may be linked to the activation of cell proliferation.

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