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 d istribution of HO-1 in human lung continue to be poorly characterized. The localization of HO-1 was studied in histopathologically healthy lung from n onsmoking patients with a carcinoid or other lung tumor (5 cases), pulmonar y sarcoidosis (13 cases), and chronic interstitial pneumonias (9 cases, usu al interstitial pneumonia; 10 cases, desquamative interstitial pneumonia). Immunostaining was graded from 0 (no immunoreactivity) to +++ (intense immu noreactivity). In healthy lung, HO-1 was localized to alveolar macrophages with reactivity varying from moderate to intense, and in bronchial epitheli um, alveolar epithelium, endothelium, and interstitium, the immunoreactivit y was not detectable or was very low. Sarcoidosis and interstitial pneumoni as showed intense HO-1 immunoreactivity in alveolar macrophages in most of the cases and weak to intense immunoreactivity in the granulomas of sarcoid osis. The immunoreactivity of interstitium was negative or weak in the fibr otic areas of the lung and also in the samples of bronchoalveolar lavage fl uid obtained from the patients with UIP. Western blotting indicated that HO -1 is up-regulated by exposure of monocytes to formylated peptide, fMLP, wh ich causes respiratory burst in the cells, and that inhibition of HO-1 by t in protoporphyrin potentiates the injury of fMLP-exposed cells. In conclusi on, these data show differential distribution of HO-I in human lung cells a nd strongly suggest the importance of HO-1, especially in the defense of al veolar macrophages in normal human lung and in the inflammatory, but not in the fibrotic, stage of interstitial lung disorders. Hum PATHOL 32: 1257-12 63. Copyright (C) 2001 by W.B. Saunders Company.