Distribution of type-1 and type-2 angiotensin receptors in the normal human lung and in lungs from patients with chronic obstructive pulmonary disease

This study was designed to examine the cellular distribution of the angiote nsin II type-1 (AT(1)) and type-2 (AT(2)) receptors in the normal human and pathological human lung. Riboprobes were prepared against specific portion s of each receptor DNA and labelled with FITC for detection using an anti-F ITC antibody in combination with the alkaline phosphatase-anti-alkaline pho sphatase technique and new Fuchsin. These were used to detect the presence of receptor mRNA in the lung. Specific antibodies were used to detect recep tor protein in cells by immunocytochemistry. Image analysis was used in ord er to semi-quantify receptor density. AT(1) receptor mRNA and protein were localised on vascular smooth muscle cells, macrophages and in the stroma un derlying the airways epithelium probably relating to underlying fibroblasts . The AT(1) receptor protein was not expressed in the epithelium although t here was a low level of mRNA. In contrast, AT(2) receptor RNA and protein w as observed in the epithelium, with strong staining on the bronchial epithe lial cell brush border and also on many of the underlying mucous glands. Th e AT(2) receptor was also present on some endothelial cells. These findings were supported by the presence of mRNA in each case. In patients with chro nic obstructive pulmonary disease, there was a five- to sixfold increase in the ratio of AT(1) to AT(2) receptors in the regions of marked fibrosis su rrounding the bronchioles. This correlated well with the reduced lung funct ion as expressed by the forced expiratory volume.