Platelet-derived growth factor in bronchiolitis obliterans-organizing pneumonia.

Bronchiolitis obliterans-organizing pneumonia (BOOP) is a disorder characterized by intraluminal proliferation of connective tissue in distal air spaces. As part of a general investigation of the role of growth factors in this process, the present study examined the expression of the mitogen, platelet-derived growth factor (PDGF), and one of its receptors, PDGFR-beta, in this disease. Serial sections of lung biopsy specimens from 20 patients with BOOP and 10 control subjects were stained with antibodies against PDGF, PDGFR-beta, and the monocyte/macrophage marker CD68. Stereologic point counting showed that PDGF+ cells represented 4.6 +/- 1.6% (mean +/- SD) of the volume occupied by lung tissue in BOOP and 2.1 +/- 0.7% in the control subjects (p < 0.0001). In both groups the positive cells were tissue macrophages, and CD68+ macrophages accounted for 10.7 +/- 4.7% of the lung tissue in BOOP as compared with 5.4 +/- 3.7% in the control subjects (p < 0.005). PDGFR-beta immunoreactivity was present in some alveolar epithelial cells in BOOP, but was absent in control subjects. We conclude that PDGF+ cells and CD68+ macrophages are found in greater numbers in lungs with BOOP, and an increased expression of PDGFR-beta epitopes was observed in some patients with BOOP. We speculate that these molecules are important in the pathogenesis of the destructive fibroproliferative process that characterizes this disease

Platelet-derived growth factor and its receptor in lungs from patients with asthma and chronic airflow obstruction.

The airway walls of patients who have asthma or chronic obstructive pulmonary disease (COPD) are thickened by an increase in the amount of smooth muscle and connective tissue. Platelet-derived growth factor (PDGF) is a candidate cytokine for this increase because it can produce smooth muscle proliferation in vitro. The present study was designed to examine the expression of PDGF and its receptor (PDGFR) in lungs from six asthmatics, six patients with COPD, and six patients with normal lung function. PDGF was immunolocalized to tissue macrophages, but the number of PDGF-positive cells was similar in all three groups. PDGFR-beta was rarely expressed on interstitial cells, and, occasionally, on bronchial epithelium. Northern blotting, performed on tissue from the same groups, showed a positive correlation of PDGF(B) with PDGFR-beta mRNA level (r = 0.74, P < 0.001) and a higher abundance of PDGF(B) and PDGFR-beta mRNA in the asthmatics vs. the COPD (P < 0.05). We conclude that PDGF and its receptor are expressed in human lungs but do not correlate closely with the structural changes in diseased airways

Selection of housekeeping genes for real-time PCR in atopic human bronchial epithelial cells

The stability of housekeeping genes (HKGs) is critical when performing real-time quantitative PCR. To date, the stability of common HKGs has not been systematically compared in human airway epithelial cells (AEC) in normal and atopic subjects. Expression levels of 12 HKGs were measured in AECs from a cohort of 30 healthy atopic nonasthmatic or atopic asthmatic children. Gene expression stability was determined using three different Visual Basic for Applications applets (geNorm, NormFinder and BestKeeper). All 12 HKGs were expressed in AECs. However, the hypoxanthine ribosyltransferase and TATA-binding protein genes were excluded from further analysis due to low expression levels. The cyclophilin A gene was ranked the most stable by all three methods. The expression levels of the β-actin and glyceraldehyde-3-phosphate dehydrogenase genes were significantly different between the three groups of patients, with atopic asthmatics showing the highest expression levels for both genes. The results suggest that the cyclophilin A gene is the most suitable housekeeping gene analysed for expression studies utilising uncultured bronchial airway epithelial cells from healthy and asthmatic children, and highlight the importance of validating housekeeping genes for each experimental model. Copyright©ERS Journals Ltd 2008

COPD phenotypes in biomass smoke – versus tobacco smoke-exposed Mexican women

We hypothesized that biomass smoke exposure is associated with an airway-predominant COPD phenotype, while tobacco-related COPD is associated with an emphysema-predominant phenotype. In this cross-sectional study, female never-smokers with COPD and biomass exposure (n=21) and female ex-cigarette smokers with COPD without biomass exposure (n=22) completed computed tomography (CT) at inspiration and expiration, pulmonary function, blood gas, exercise tolerance, and quality of life measures. Two radiologists scored the extent of emphysema and air trapping on CT. Quantitative emphysema severity and distribution, and airway wall thickness were calculated using specialized software. Women in the tobacco group had significantly more emphysema than the biomass group (radiologist score 2·3 vs 0·7, p=0·001; % emphysema on CT scan 27% vs 19%, p=0·046; and a larger size of emphysematous spaces, p=0·006). Women in the biomass group had significantly more air trapping than the tobacco group (radiologist score = 2·6 and 1·5 respectively; p=0·02) and also scored lower on the symptom, activities and confidence domains of quality of life and had lower oxygen saturation at rest and during exercise (p<0·05). Biomass smoke exposure is associated with less emphysema but more air trapping than tobacco smoke exposure, suggesting an airway-predominant phenotype.Medicine, Faculty ofOther UBCNon UBCMedicine, Department ofPhysical Therapy, Department ofRadiology, Department ofReviewedFacultyResearche