Expression and regulation of hemeoxygenase 1 in healthy human lung and interstitial lung disorders

Hemeoxygenase 1 (HO-1) has been implicated in the protection of lung tissue against exogenous oxidant exposure. However, the expression and cellular distribution of HO-1 in human lung continue to be poorly characterized. The localization of HO-1 was studied in histopathologically healthy lung from nonsmoking patients with a carcinoid or other lung tumor (5 cases), pulmonary sarcoidosis (13 cases), and chronic interstitial pneumonias (9 cases, usual interstitial pneumonia; 10 cases, desquamative interstitial pneumonia). Immunostaining was graded from 0 (no immunoreactivity) to +++ (intense immunoreactivity). In healthy lung, HO-1 was localized to alveolar macrophages with reactivity varying from moderate to intense, and in bronchial epithelium, alveolar epithelium, endothelium, and interstitium, the immunoreactivity was not detectable or was very low. Sarcoidosis and interstitial pneumonias showed intense HO-1 immunoreactivity in alveolar macrophages in most of the cases and weak to intense immunoreactivity in the granulomas of sarcoidosis. The immunoreactivity of interstitium was negative or weak in the fibrotic areas of the lung and also in the samples of bronchoalveolar lavage fluid obtained from the patients with UIP. Western blotting indicated that HO-1 is up-regulated by exposure of monocytes to formylated peptide, fMLP, which causes respiratory burst in the cells, and that inhibition of HO-1 by tin protoporphyrin potentiates the injury of fMLP-exposed cells. In conclusion, these data show differential distribution of HO-1 in human lung cells and strongly suggest the importance of HO-1, especially in the defense of alveolar macrophages in normal human lung and in the inflammatory, but not in the fibrotic, stage of interstitial lung disorders.