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

Abstract

This study was designed to examine the cellular distribution of the angiotensin II type-1 (AT1) and type-2 (AT2) receptors in the normal human and pathological human lung. Riboprobes were prepared against specific portions of each receptor DNA and labelled with FITC for detection using an anti-FITC antibody in combination with the alkaline phosphatase-anti-alkaline phosphatase technique and new Fuchsin. These were used to detect the presence of receptor mRNA in the lung. Specific antibodies were used to detect receptor protein in cells by immunocytochemistry. Image analysis was used in order to semi-quantify receptor density. AT1 receptor mRNA and protein were localised on vascular smooth muscle cells, macrophages and in the stroma underlying the airways epithelium probably relating to underlying fibroblasts. The AT1 receptor protein was not expressed in the epithelium although there was a low level of mRNA. In contrast, AT2 receptor RNA and protein was observed in the epithelium, with strong staining on the bronchial epithelial cell brush border and also on many of the underlying mucous glands. The AT2 receptor was also present on some endothelial cells. These findings were supported by the presence of mRNA in each case. In patients with chronic obstructive pulmonary disease, there was a five- to sixfold increase in the ratio of AT1 to AT2 receptors in the regions of marked fibrosis surrounding the bronchioles. This correlated well with the reduced lung function as expressed by the forced expiratory volume.

Mast cell renin and a local renin–angiotensin system in the airway: Role in bronchoconstriction

“…Components of RAS have been identified in lung tissue, including aogen mRNA (6,7), and angiotensin-converting enzyme (ACE), the pulmonary endothelium being the primary source for ACE in the body (8). ANG II receptors are also expressed in lung tissue, with the ANG II type 1 receptor (AT 1 R) subtype found on bronchial smooth muscle cells (9) and ANG II type 2 receptor (AT 2 R) observed on the bronchial epithelial cell brush border (10). An intrapulmonary source of renin protein has not yet been identified.…”

Specific single chain variable fragment (ScFv) antibodies to angiotensin II AT2 receptor: evaluation of the angiotensin II receptor expression in normal and tumor-bearing mouse lung

“…In adult human lung tissues, AT 2 protein expression was detected in brush borders of bronchial epithelium by immunohistochemical analysis with anti-rabbit anti-AT 2 antiserum (Bullock et al 2001). On the contrary, our newly developed recombinant antibodies detected weak but clear signals of AT 2 protein expression in the alveolar epithelial cells and bronchial epithelium of adult mouse lung.…”

“…With regard to overall Ang II signaling and lung cancer, AT 1 -mediated Ang II signaling should be taken into a consideration since the AT 1 is the major Ang II receptor and its expression in the lung tissue is relatively abundant (Bullock et al 2001). In our study, a small amount of the AT 1 expression was detected in normal alveolar epithelium and this expression was markedly increased in NNK-induced adenomatous epithelial cells (Fig.…”

“…There are only a few studies elucidating the expression of AT 2 in the lung tissues (Bullock et al 2001;Chassagne et al 2000). Although an earlier study has demonstrated that the AT 2 protein is abundantly expressed in bronchial epithelium brush border and mucus glands in human lung tissues (Bullock et al 2001), this expression pattern appears to not be associated with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced adenoma development since NNK-induced adenocarcinoma appears to originate in type II pneumocytes (Hecht 1998).…”

Increased frequency of the angiotensin-converting enzyme gene D-allele is associated with noninfectious pulmonary dysfunction following allogeneic stem cell transplant

“…Although we did not investigate the relationship between serum or BAL fluid ACE levels and the development of NIPD, the results of the present study are consistent with previous findings for the existence of a pulmonary renin-angiotensin system and the capacity for A-II generation within the lung. These findings include the demonstration of high A-II levels in the normal rat lung, 14 the expression of angiotensinogen and A-II type 1 receptors in lung tissue, 15 and the presence of elevated bronchoalveolar lavage fluid and/or serum ACE levels in several potentially fibrotic lung diseases. 16,17 In experimental lung injury models induced by bleomycin, A-II stimulates lung fibroblast procollagen production via the AT1 receptor, and the autocrine production of TGF-b is a potent inducer of fibroblast procollagen synthesis.…”