Extracellular Superoxide Dismutase mRNA Expressions in the Human Lung by in Situ Hybridization

The extracellular form of superoxide dismutase (EC-SOD), SOD3, is contained in the human lung in relatively high amounts when compared to other organs. It has not been previously shown whether or not EC-SOD is synthesized and secreted by specific lung cells. We examined the expression of EC-SOD mRNA in human lung cells by in situ hybridization using a digoxigenin-labeled EC-SOD cRNA probe. Strong signals of EC-SOD synthesis were found in the epithelium of all airways. Secretory and basal cells, but not ciliated cells, were labeled for EC-SOD mRNA. Expression of EC-SOD mRNA was found in endothelial cells lining both arteries and veins. Many cells in the alveolar septum exhibited strong expression of EC-SOD mRNA. In addition, epithelial cells lining the outer wall of intrapulmonary airways and vessels were heavily labeled for EC-SOD mRNA. The lung parenchymal epithelial cells containing EC-SOD mRNA were identified as alveolar type II cells by colocalization with surfactant protein-A. Human alveolar macrophages were found to contain a substantial amount of EC-SOD mRNA expression. Alveolar type I epithelial cells and capillary endothelial cells did not display detectable signals of EC-SOD mRNA. Smooth muscle cells in muscular arteries were not labeled by the EC-SOD mRNA probe. These results show that airway epithelial cells and alveolar type II cells are the major cell types that synthesize fibroblasts EC-SOD in the human lung. EC-SOD has been shown by immunocytochemistry to be associated with the extracellular matrix around airway epithelium and in the walls of intrapulmonary arterioles. The site of EC-SOD localization, therefore, is closely related to the site of its synthesis.