TRANSFORMING GROWTH-FACTOR-BETA-1 (TGF-BETA-1) GENE-EXPRESSION BY EOSINOPHILS IN ASTHMATIC AIRWAY INFLAMMATION

The increase in thickness of bronchial walls by such structural change s as subepithelial fibrosis contributes to the severity and chronicity of asthma by amplifying airway narrowing. However, the pathogenesis o f this structural alteration is not known. Transforming growth factor beta 1 (TGF beta 1) is known to have biologic activities relevant to t he cellular and molecular events in subepithelial fibrosis, such as th e deposition of collagen I and III and the increase of myofibroblasts beneath the epithelial basement membrane. Therefore, we examined TGF b eta 1 gene expression in bronchial biopsy tissues from five severe ast hmatics, five mild asthmatics, and five normal subjects using in situ hybridization combined with histochemical staining. Cells expressing T GF beta 1 mRNA were detected in tissues from four normal subjects,one mild asthmatic, and five severe asthmatics. The density of positive ce lls in severe asthmatic tissues (52.1 +/- 22.7, mean +/- SD/mm(2)) was significantly greater than that in mild asthmatic tissues (1.0 +/- 1. 9/mm(2), P < 0.01) or normal tissues (10.5 +/- 10.6/mm(2), P < 0.02). The density in mild asthmatic tissues was not significantly different from that in normal tissues. The vast majority of positive cells in se vere (99.1 +/- 1.7%) and mild (100%) asthmatic tissues were identified as eosinophils. In contrast, eosinophils constituted a small portion of positive cells (20.8 +/- 21.6%) in normal tissues. These results in dicated that TGF beta 1 mRNA was overexpressed in severe asthmatics an d that the main source of the mRNA was eosinophils, suggesting that eo sinophils play an important role in the pathogenesis not only of infla mmation but also of structural changes, such as subepithelial fibrosis , in asthmatic airways.