IMMUNOCYTOCHEMICAL LOCALIZATION OF EXTRACELLULAR-SUPEROXIDE DISMUTASEIN HUMAN LUNG

BACKGROUND: Extracellular superoxide dismutase (EC-SOD) is a principal enzymatic scavenger of the superoxide anion in extracellular spaces. It is thought to be important as a defense against superoxide-mediated damage to both cell surfaces and extracellular matrix proteins. EC-SO D may also be important in regulating intercellular signalling by extr acellular superoxide. EC-SOD is believed to be mainly located in the e xtracellular matrix of tissues. However, the specific localization of EC-SOD is unknown. Knowledge of the distribution of EC-SOD is an essen tial step in defining its functions. EXPERIMENTAL DESIGN: Using light microscopic immunohistochemistry, electron microscopic immunocytochemi stry and an EC-SOD affinity-purified polyclonal rabbit antibody to hum an recombinant EC-SOD, we evaluated the distribution of EC-SOD in huma n lungs. RESULTS: These studies revealed that in the lung EC-SOD is pr imarily located in the extracellular matrix. Specifically, EC-SOD is f ound in areas containing high amounts of type I collagen and other uni dentified matrix elements, but was not seen in areas rich in elastin o r cartilage. In the lung, EC-SOD is predominantly located around large r vessels and airways, and, to a lesser degree, in the extracellular m atrix around alveolar and capillary regions. Some EC-SOD was found in bronchiolar epithelial cell junctions and around the surface of vascul ar and airway smooth muscle cells. No labeling was seen on endothelial cell surfaces of capillaries, small muscular, or large elastic vessel s in the lung. Labeling for EC-SOD was limited to the extracellular sp aces, consistent with it being a secreted protein, with the exception of a small amount of intracellular labeling seen in bronchial epitheli al cells and type II cells. CONCLUSIONS: The labeling distribution of EC-SOD in human lungs was defined using immunohistochemistry and immun ocytochemical techniques. The findings suggest that EC-SOD is not diff usely located throughout the lung, but has a specific distribution in the extracellular matrix. These findings on the distribution of EC-SOD suggest that specific roles for EC-SOD may include the protection of matrix elements such as collagen from oxidative stress and that it may also function in the regulation of intercellular signals that are mod ulated by reactive oxygen species.