CELLULAR-DISTRIBUTION OF C-JUN AND C-FOS IN RAT LUNG BEFORE AND AFTERBLEOMYCIN-INDUCED INJURY

C-Jun and c-Fos transcription factors have been associated with enhanc ed cellular proliferation. We studied their cellular distribution in n ormal and fibrotic rat lung. Pulmonary fibrosis was induced by intratr acheal administration of bleomycin. In normal rat lung, c-dun and c-Fo s are present in alveolar macrophages and type II pneumocytes, in the bronchiolar epithelium and in smooth muscle cells of bronchioli and bl ood vessels. Subcellular fractionation of proteins revealed a predomin ant presence of both c-dun and c-Fos in the heavy membrane fraction co ntaining mitochondria and secretory granules. This was confirmed by im munoelectron microscopy. which also revealed a different localization of c-Jun and c-Fos in different cell types. Whereas in type LI pneumoc ytes and in macrophages cytoplasmic c-Jun and c-Fos is associated with mitochondria, in Clara cells of the bronchial epithelium only secreto ry granules contain c-Jun and c-Fos. In addition, c-Jun is strongly pr esent in the nuclear fraction. In the fibrotic rat lung c-Jun and c-Fo s are located in the same cell types as in control lungs. In addition, fibroblasts contain c-dun and c-Fos in areas of proliferation whereas in areas of complete fibrosis then is only a very weak expression of c-Jun and c-Fos.