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Am. J. Respir. Crit. Care Med., Volume 158, Number 6, December 1998, 1951-1957

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

WILLEM I. de BOER, ANNEMARIE van SCHADEWIJK, JACOB K. SONT, HARI S. SHARMA, JAN STOLK, PIETER S. HIEMSTRA, and J.HAN J. M. van KRIEKEN

Departments of Pulmonology and Pathology, Leiden University Medical Center, Leiden, and Department of Pharmacology, Erasmus University, Rotterdam, The Netherlands

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 beta 1 (TGF-beta 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 TGF-beta 1, TGF-beta receptors type I and II (TGF-beta RI and TGF-beta RII) by immunohistochemistry and mRNA in situ hybridization in peripheral lung tissue of 14 current or ex-smokers with COPD (FEV1 < 75%) and 14 without COPD (FEV1 > 84%). In both groups, TGF-beta 1 and its receptors are present in airway and alveolar epithelial cells, airway and vascular smooth muscle cells, and tissue and alveolar CD68+ cells (considered herein to be macrophages). In subjects with COPD, a semiquantitative analysis revealed approximately twofold higher levels of TGF-beta 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 TGF-beta 1 mRNA and protein expression (r = 0.62; p < 0.002), and between the FEV1 of all subjects together and TGF-beta 1 protein (r = -0.60; p < 0.0002) and mRNA (r = -0.67; p < 0.002) levels. The epithelial expression of TGF-beta 1 mRNA and TGF-beta 1 protein correlates with the number of intraepithelial macrophages (both: r = 0.44; p < 0.03) whereas intraepithelial mast cell numbers correlate with epithelial TGF-beta 1 mRNA expression. These data suggest a role for TGF-beta 1 in recruiting macrophages into the airway epithelium in COPD.




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