Expression of transforming growth factors beta (1, 2, 3) and connective tissue growth factor in the peripheral lung from GOLD stage 1-2 COPD patients and smokers with normal lung function

Transforming growth factor (TGF)-ß1 is highly expressed in epithelium and macrophages of small airways in patients with chronic obstructive pulmonary disease (COPD). It is a potent inducer of fibrosis, partly via the release of the potent fibrogenic mediator, connective tissue growth factor (CTGF). Two other members (2 and 3) of TGF family may also be pro-fibrogenics in vitro. However, the expression of TGF2 and 3, and CTGF in the peripheral lung of patients with mild to moderate chronic obstructive pulmonary disease (COPD) has not been previously studied. We have investigated the expression of TGF1, 2, 3, and CTGF in lung parenchyma of smokers with mild to moderate (GOLD stages 1 and 2) COPD (n=16) compared with age-matched smokers with normal lung function (n=18). Peripheral lung tissue was obtained during lung resection surgery. We examined formalin-fixed paraffin-embedded lung sections. By immunohistochemistry (IHC) we detected TGF1, 2, 3, and CTGF expression mainly in bronchiolar epithelial cells and macrophages. The semiquantitative IHC scoring for TGF1, 2, 3, and CTGF in bronchiolar epithelial cells and endoalveolar macrophages was not significantly different between COPD patients and smokers with normal lung function. These data suggest that TGF1, 2, 3, and CTGF expression are not increased in the peripheral lung of GOLD stage 1 and 2 COPD patients

Heat shock proteins 70 and 90 expression in peripheral lung of COPD patients

Heat shock proteins (HSP) 70 and 90 are chaperones that play critical roles in many cellular functions. Peripheral lung (small airways and lung parenchyma) is the main site of airflow obstruction in chronic obstructive pulmonary disease (COPD). In animal models HSP-70 and -90 may have roles in the pathogenesis of pulmonary fibrosis and MUC5AC secretion. The aim of our study was to investigate by immunohistochemistry the localization and expression of HSP-70 and -90 in the peripheral lung of smokers with or without COPD compared with non-smoker subjects. Lung tissue was obtained during lung resection surgery. We examined formalin-fixed paraffin-embedded lung sections by immunohistochemistry for identification of HSP-70 and -90+ cells. The number of HSP +ve cells was determined among the alveolar macrophages and in the bronchiolar epithelium. Samples from 8 non-smokers subjects (age: 69.1±3.2, 1M, FEV1/FVC ratio = 80.1±2.3), 26 smokers with normal lung function (age: 67.9±2.3, 22M, 48±9 pack years, FEV1/FVC ratio=77.5±1.3) and 19 smokers with COPD (age: 71.3±1.4, 17M, 45±8 pack years, post-bronchodilator FEV1/FVC ratio=60.1±2.7) were analyzed. We found a significant difference in HSP-90 +ve alveolar macrophages numbers between non-smokers (35.6±9.4% +ve alveolar macrophages/total number alveolar macrophages) and smokers with normal lung function (69.0±5.7% +ve alveolar macrophages/total number alveolar macrophages; p<0.05) but not between non-smokers and smokers with COPD (57.3±7.7% +ve alveolar macrophages/total number alveolar macrophages) nor between smokers with normal lung function and smokers with COPD. No differences were found in HSP-70 expression in the alveolar macrophages. Also, HSP-70 and -90 expression was similar in the bronchiolar epithelium of the 3 groups of subjects. These data indicates HSP-90 is up-regulated in the alveolar macrophages of smokers with normal lung function

MUC5AC and MUC5B expression in central airways from non-smokers, smokers with normal lung function and GOLD stage 1 and 2 COPD patients

Mucus expectoration is a common feature of chronic obstructive pulmonary disease (COPD). Sputum is mainly produced in central airways. The two major mucins in sputum are MUC5AC and MUC5B. The major site of mucus production in central airways is represented by the submucosal glands. The expression of MUC5AC and MUC5B in bronchial epithelium and submucosal glands from patients with COPD is not known. We investigated by immunohistochemistry (IHC) the expression of MUC5B and MUC5AC in bronchial rings (obtained at lung resection surgery) from 10 asymptomatic non-smoking subjects, twenty smokers with normal lung function and twenty smokers with COPD. Quantitative analysis of the immunohistochemical staining of bronchial epithelial cells and submucosal glands was performed using dedicated computerised digital software. The total area covered by MUC5AC +ve cells in the bronchial epithelium was increased in smokers (with and without COPD) (66.1 ± 5.7% total epithelial area) compared to non-smoking subjects (21.2 ± 7.1%; p<0.01). The total area covered by MUC5AC+ve cells in the bronchial submucosal glands was significantly higher in patients with COPD (22.2 ± 5.5% total gland area) compared to smokers with normal lung function (10.6 ± 2.1%; p<0.05) and non-smoking subjects (5.9 ± 3.5%; p<0.05). MUC5B expression was not significantly different between groups both in bronchial epithelium and submucosal glands. These results suggest that COPD is associated with increased expression of MUC5AC in the bronchial airways, particularly in bronchial glands. This may be involved in the pathogenesis of the disease

MUC5AC expression is increased in bronchial submucosal glands of stable COPD patients

AIMS: Mucus expectoration is a common feature of chronic obstructive pulmonary disease (COPD). MUC5AC and MUC5B, the major mucins, are released predominantly from submucosal glands in the central airways. The aim was to investigate gland size and MUC5AC and MUC5B expression in bronchial rings from smokers with COPD compared with control groups. METHODS AND RESULTS: Bronchial rings from 10 non-smoking subjects, 20 smokers with normal lung function and 20 smokers with COPD were studied. Periodic acid-Schiff (PAS) and Alcian blue histochemistry and MUC5AC and MUC5B immunohistochemistry followed by quantification of the immunoreactive area was performed. The area occupied by MUC5AC+ cells in bronchial submucosal glands was increased in COPD [20% (5.5-31.7%) gland area] compared with smokers with normal lung function [9.5% (2.5-17.5%); P < 0.05] and non-smoking subjects [2% (0.4-6.2%); P < 0.05]. The area occupied by MUC5AC+ cells in the bronchial surface epithelium was also increased in smokers (with/without COPD) [73.5% (25-92%) epithelial area] compared with non-smoking subjects [15% (2.7-32%); P < 0.01]. Gland size, PAS, Alcian blue staining and MUC5B expression were not significantly different among groups. MUC5AC expression correlated with the degree of airflow obstruction. MUC5AC and MUC5B expression correlated with pack-years. CONCLUSIONS: COPD is associated with increased MUC5AC expression in submucosal glands, indicating that MUC5AC may be involved in the pathophysiology of the disease

MUC5AC expression is increased in bronchial submucosal glands of stable COPD patients.

AIMS: Mucus expectoration is a common feature of chronic obstructive pulmonary disease (COPD). MUC5AC and MUC5B, the major mucins, are released predominantly from submucosal glands in the central airways. The aim was to investigate gland size and MUC5AC and MUC5B expression in bronchial rings from smokers with COPD compared with control groups. METHODS AND RESULTS: Bronchial rings from 10 non-smoking subjects, 20 smokers with normal lung function and 20 smokers with COPD were studied. Periodic acid-Schiff (PAS) and Alcian blue histochemistry and MUC5AC and MUC5B immunohistochemistry followed by quantification of the immunoreactive area was performed. The area occupied by MUC5AC+ cells in bronchial submucosal glands was increased in COPD [20% (5.5-31.7%) gland area] compared with smokers with normal lung function [9.5% (2.5-17.5%); P < 0.05] and non-smoking subjects [2% (0.4-6.2%); P < 0.05]. The area occupied by MUC5AC+ cells in the bronchial surface epithelium was also increased in smokers (with/without COPD) [73.5% (25-92%) epithelial area] compared with non-smoking subjects [15% (2.7-32%); P < 0.01]. Gland size, PAS, Alcian blue staining and MUC5B expression were not significantly different among groups. MUC5AC expression correlated with the degree of airflow obstruction. MUC5AC and MUC5B expression correlated with pack-years. CONCLUSIONS: COPD is associated with increased MUC5AC expression in submucosal glands, indicating that MUC5AC may be involved in the pathophysiology of the disease