LOSS OF CAVEOLIN EXPRESSION IN TYPE-I PNEUMOCYTES AS AN INDICATOR OF SUBCELLULAR ALTERATIONS DURING LUNG FIBROGENESIS

Caveolin is a major structural protein of caveolae, also known as plas malemmal vesicles, which are particularly abundant in type I pneumocyt es and capillary endothelial cells of lung parenchyma. Here we demonst rate that caveolin expression in the alveolar epithelium of rats and m ini pigs is strikingly downregulated after irradiation-induced lung in jury. Indirect immunoperoxidase staining with polyclonal anti-caveolin antibodies, confirmed by double fluorescence studies with type I cell -specific monoclonal anti-cytokeratin antibodies or lectins, revealed a dramatic loss of caveolin immunoreactivity in type I pneumocytes. Ln contrast, caveolin expression increased in endothelial cells. Immunob lotting of lung homogenates from normal and irradiated rats using spec ific anti-caveolin antibodies confirmed the presence of caveolin in no rmal tissue and its marked decrease of expression in fibrotic tissue. The loss of caveolin as an important structural protein of caveolae in alveolar epithelial cells may be an early indicator of serious type I cell injury during fibrogenesis. The increase of caveolin immunoreact ivity in endothelia of blood vessels may indicate that different types of caveolae and/or different regulatory mechanisms of caveolin expres sion exist.