Cellular distribution of c-Jun and c-Fos in rat lung before and after bleomycin induced injury.

C-Jun and c-Fos transcription factors have been associated with enhanced cellular proliferation. We studied their cellular distribution in normal and fibrotic rat lung. Pulmonary fibrosis was induced by intratracheal administration of bleomycin. In normal rat lung, c-Jun and c-Fos are present in alveolar macrophages and type II pneumocytes, in the bronchiolar epithelium and in smooth muscle cells of bronchioli and blood vessels. Subcellular fractionation of proteins revealed a predominant presence of both c-Jun and c-Fos in the heavy membrane fraction containing mitochondria and secretory granules. This was confirmed by immunoelectron microscopy, which also revealed a different localization of c-Jun and c-Fos in different cell types. Whereas in type II pneumocytes and in macrophages cytoplasmic c-Jun and c-Fos is associated with mitochondria, in Clara cells of the bronchial epithelium only secretory granules contain c-Jun and c-Fos. In addition, c-Jun is strongly present in the nuclear fraction. In the fibrotic rat lung c-Jun and c-Fos are located in the same cell types as in control lungs. In addition, fibroblasts contain c-Jun and c-Fos in areas of proliferation whereas in areas of complete fibrosis there is only a very weak expression of c-Jun and c-Fos.