Respiratory epithelium

About: Respiratory epithelium is a research topic. Over the lifetime, 5048 publications have been published within this topic receiving 222304 citations. The topic is also known as: respiratory tract epithelium & Respiratory Mucosa.

Cellular response in naphthalene-induced Clara cell injury and bronchiolar epithelial repair in mice

Abstract: Clara cells, progenitors for bronchiolar epithelium, are also primary targets for metabolically activated pulmonary cytotoxicants and have an abundance of the cytochrome P-450 monooxygenases required for xenobiotic metabolism. To define the repair pattern after massive Clara cell injury, mice were treated with naphthalene, and lungs evaluated 1-14 days postinjury (DPI). Clara cells of terminal bronchioles were vacuolated and swollen 1 DPI, exfoliated 2 DPI, and resembled controls at 14 DPI. The volume fraction of vacuolated cells was highest 1 and 2 DPI and minimal at 5-7 DPI. The volume fraction of normal nonciliated cells decreased 40% at 1 DPI. Cell proliferation increased within epithelium and interstitium at 1 DPI, was maximal at 2 DPI, and at all other time points was similar to baseline levels. Expression of Clara cell differentiation markers was barely detectable in terminal bronchiolar epithelium at 1 and 2 DPI, clearly detectable at 4 DPI, and gradually returned to control levels at 5-14 DPI. We conclude that bronchiolar epithelial repair after naphthalene injury involves distinct phases of proliferation and differentiation, proliferation of cells that are not differentiated Clara cells, and interaction of multiple cell types including nontarget cells.

Immunohistochemical detection of NAD(P)H:quinone oxidoreductase in human lung and lung tumors

Abstract: NAD(P)H:quinone oxidoreductase (NQO1) is a flavoenzyme that catalyzes the two-electron reduction of quinones and related compounds. With the use of biochemical assays, NQO1 has been shown to be overexpressed in many types of cancer, including non-small cell lung cancer (NSCLC). NQO1 can bioactivate antitumor quinones such as mitomycin C, and new quinone-based drugs are currently being developed to target this enzyme in tumors such as NSCLC. Because there is no information on the cell-specific expression of NQO1 in lung, the purpose of this study was to examine the expression of NQO1 in human NSCLC, small cell lung cancer, carcinoid lung tumors, and normal lung using immunohistochemistry. A high level of NQO1 protein expression was detected by immunohistochemistry in NSCLC (adenocarcinoma, squamous cell carcinoma, and bronchoalveolar carcinoma), but no NQO1 protein could be detected in small cell lung cancer or carcinoid lung tumors. In addition, NQO1 protein expression was examined by immunohistochemistry in normal lung tissue. A high level of NQO1 protein expression was detected by immunohistochemistry in normal lung respiratory epithelium, with the highest levels of expression observed in ciliated columnar epithelial cells. Significant amounts of NQO1 protein were also detected in the vascular endothelium and adipocytes. These data demonstrate that NQO1 is overexpressed in NSCLC. Cells in normal lung also contain marked NQO1 protein and may be damaged by drugs activated by NQO1. These data validate NSCLC as a target for NQO1-directed agents and suggest that the potential for lung toxicity be considered in the preclinical development of quinone-based antitumor drugs.

Reduced Epithelial Expression of Secretory Component in Small Airways Correlates with Airflow Obstruction in Chronic Obstructive Pulmonary Disease

Abstract: The epithelial polymeric immunoglobulin receptor/transmembrane secretory component (pIgR/SC) transports into secretions polymeric immunoglobulin A (pIgA), which is considered the first line of defense of the respiratory tract. The present study, done with quantitative immunohistochemistry, evaluated epithelial expression of secretory component (SC) and Clara cell protein (CC16) and neutrophil infiltration into the airways of eight patients with severe chronic obstructive pulmonary disease (COPD) who were undergoing lung transplantation, as compared with these processes in six nonsmoking patients with pulmonary hypertension who were used as controls and in lung specimens from five smokers without chronic bronchitis. Staining for SC was significantly decreased in the COPD patients as compared with the controls, both in large (mean optical density [MOD]: 23.4 [range: 21.1 to 27.8] versus 42.2 [range: 28.2 to 49.3], p = 0.003) and in small airways (MOD: 30.8 [range: 20.3 to 39.4] versus 41.5 [range: 39.2 to 46.2], p = 0.003). SC expression in small airways correlated strongly with functional parameters such as FEV1 (Kendall's tau (K) = 0.76, p = 0.008), FVC (K = 0.64, p = 0.03), and midexpiratory flow at 50% of VC (MEF50) (K = 0.74, p = 0.01). The reduced expression of SC in large airways correlated with neutrophil infiltration in submucosal glands (K = -0.47, p = 0.03). Expression of CC16 in the bronchial epithelium of COPD patients was also significantly decreased as compared with that of controls, especially in small airways (MOD: 28.3 [range: 26.8 to 32.4] versus 45.8 [range: 40.7 to 56.0], p = 0.002), but no correlation was observed with lung function tests. In conclusion, this study shows that reduced expression of SC in airway epithelium is associated with airflow obstruction and neutrophil infiltration in severe COPD.

Elevated expression of endothelin-1 and endothelin-converting enzyme-1 in idiopathic pulmonary fibrosis: possible involvement of proinflammatory cytokines.

Abstract: Endothelin-1 (ET-1) is a vasoconstrictor, bronchoconstrictor, and mitogenic peptide which is enzymatically converted from a biologically inactive big ET to mature ET (21 amino acid) by the ET-converting enzyme (ECE). Here, we investigate the expression of ECE-1, big ET-1, and ET-1 in the lungs of patients with idiopathic pulmonary fibrosis (IPF) and compare it to those of normal subjects using immunohistochemistry and in situ hybridization. In normal lungs, focal moderate expression of all three molecules is localized to airway epithelium, pulmonary endothelium, and airway and vascular smooth muscle cells. Serous bronchial glands also expressed ET-1 and ECE-1. In IPF, strong diffuse expression of ECE-1 was seen in airway epithelium, proliferating type II pneumocytes, and in endothelial and inflammatory cells. ECE-1 immunostaining was colocalized to big ET-1 and ET-1 immunostaining, and correlated with disease activity (P < 0.05). To study regulatory mechanisms of ET-1 and ECE-1 expression, human normal bronchial epithelial (NBE) cells were treated with cytokines and analyzed by radioimmunoassay and Northern blot. Incubation of human NBE cells with IL-1alpha and -beta or tumor necrosis factor alpha (TNFalpha) resulted in a significant increase in ET-1 release and mRNA expression. TNFalpha resulted in a significant increase in ECE-1 mRNA expression. These findings demonstrated the colocalization of the precursor and active ET-1, and ECE-1 in the same cell, and that ECE-1 expression is elevated in IPF. In addition, increased expression of ET-1 and ECE-1 in IPF may be mediated by proinflammatory cytokines.

Gene transfer into the airway epithelium of animals by targeting the polymeric immunoglobulin receptor.

Abstract: Genes of interest can be targeted specifically to respiratory epithelial cells in intact animals with high efficiency by exploiting the receptor-mediated endocytosis of the polymeric immunoglobulin receptor. A DNA carrier, consisting of the Fab portion of polyclonal antibodies raised against rat secretory component covalently linked to poly-L-lysine, was used to introduce plasmids containing different reporter genes into airway epithelial cells in vivo. We observed significant levels of luciferase enzyme activity in protein extracts from the liver and lung, achieving maximum values of 13,795 +/- 4,431 and 346,954 +/- 199,120 integrated light units (ILU) per milligram of protein extract, respectively. No luciferase activity was detected in spleen or heart, which do not express the receptor. Transfections using complexes consisting of an irrelevant plasmid (pCMV lacZ) bound to the bona fide carrier or the expression plasmid (pGEMluc) bound to a carrier based on an irrelevant Fab fragment resulted in background levels of luciferase activity in all tissues examined. Thus, only tissues that contain cells bearing the polymeric immunoglobulin receptor are transfected, and transfection cannot be attributed to the nonspecific uptake of an irrelevant carrier-DNA complex. Specific mRNA from the luciferase gene was also detected in the lungs of transfected animals. To determine which cells in the lungs are transfected by this method, DNA complexes were prepared containing expression plasmids with genes encoding the bacterial beta-galactosidase or the human interleukin 2 receptor. Expression of these genes was localized to the surface epithelium of the airways and the submucosal glands, and not the bronchioles and alveoli. Receptor-mediated endocytosis can be used to introduce functional genes into the respiratory epithelium of rats, and may be a useful technique for gene therapy targeting the lung.