Transforming growth factor beta(1) and recruitment of macrophages and mastcells 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 epith elium in COPD contains increased numbers of macrophages and mast cells. Tra nsforming growth factor beta(1) (TCF-beta(1)) may be involved in this influ x because it has chemotactic activity for macrophages and mast cells. In th is study, we examined expression patterns of TGF-beta(1), TGF-beta receptor s 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-sm okers with COPD (FEV1 < 75%) and 14 without COPD (FEV1 > 84%). In both grou ps, TGF-beta(1) and its receptors are present in airway and alveolar epithe lial cells, airway and vascular smooth muscle cells, and tissue and alveola r CD68(+) cells (considered herein to be macrophages). In subjects with COP D, a semiquantitative analysis revealed approximately twofold higher levels of TCF-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) mR NA and protein expression (r = 0.62; p < 0.002), and between the FEV1 of al l subjects together and TCF-beta(1) protein (r = -0.60; p < 0.0002) and mRN A (r = -0.67; p ( 0.002) levels. The epithelial expression of TCF-beta(1) m RNA and TCF-beta(1) protein correlates with the number of intraepithelial m acrophages (both: r = 0.44; p < 0.03) whereas intraepithelial mast cell num bers correlate with epithelial TCF-beta(1) mRNA expression. These data sugg est a role for TCF-beta(1) in recruiting macrophages into the airway epithe lium in COPD.