Transforming Growth Factor b 1 and Recruitment of Macrophages and Mast Cells in Airways in Chronic Obstructive Pulmonary Disease

Chronic airways inflammation is one of the features of chronic obstructive pulmonary disease (COPD). We demonstrated previously that bronchiolar epithelium in COPD contains increased numbers of macrophages and mast cells. Transforming growth factor b 1 (TGFb 1 ) may be involved in this influx because it has chemotactic activity for macrophages and mast cells. In this study, we examined expression patterns of TGFb 1 , TGFb receptors type I and II (TGFb RI and TGFb RII) by immunohistochemistry and mRNA in situ hybridization in peripheral lung tissue of 14 current or ex-smokers with COPD (FEV 1 , 75%) and 14 without COPD (FEV 1 . 84%). In both groups, TGFb 1 and its receptors are present in airway and alveolar epithelial cells, airway and vascular smooth muscle cells, and tissue and alveolar CD68 1 cells (considered herein to be macrophages). In subjects with COPD, a semiquantitative analysis revealed approximately twofold higher levels of TGFb 1 mRNA and protein in bronchiolar and alveolar epithelium (p , 0.02) as compared with subjects without COPD. With regard to bronchiolar epithelial cells, we found a significant correlation between TGFb 1 mRNA and protein expression (r 5 0.62; p , 0.002), and between the FEV 1 of all subjects together and TGFb 1 protein (r 5 2 0.60; p , 0.0002) and mRNA (r 5 2 0.67; p , 0.002) levels. The epithelial expression of TGFb 1 mRNA and TGFb 1 protein correlates with the number of intraepithelial macrophages (both: r 5 0.44; p , 0.03) whereas intraepithelial mast cell numbers correlate with epithelial TGFb 1 mRNA expression. These data suggest a role for TGFb 1 in recruiting macrophages into the airway epithelium in COPD. de Boer WI, van Schadewijk A, Sont JK, Sharma HS, Stolk J, Hiemstra PS, van Krieken JHJM. Transforming growth factor b 1 and recruitment of macrophages and mast cells in airways in chronic obstructive pulmonary disease. AM J RESPIR CRIT CARE MED 1998;158:1951–1957.

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