Expression of c-erbB receptors and ligands in human bronchial mucose

The epidermal growth factor receptor (EGFR, c-erbB1) plays a pivotal role i n maintenance and repair of epithelial tissues; however, little is known ab out coexpression of c-erbB receptors and their ligands in human bronchial e pithelium. We therefore analyzed the expression of these molecules in cultu red bronchial epithelial cells and normal bronchial mucosa, using reverse t ranscription-polymerase chain reaction (RT-PCR), flow cytometry, and immuno histochemistry. Messenger RNA (mRNA) encoding EGFR, c-erbB2, and c-erbB3, b ut not c-erbB4, was detected in primary cultures of human bronchial epithel ial cells, as well as in the human bronchial epithelial-derived cell lines H292 and 16HBE 14(o)(-). Transcripts encoding epidermal growth factor (EGF) , heparin binding epidermal growth factor (HB-EGF), transforming growth fac tor-alpha (TGF-alpha), and amphiregulin (AR) were also detected, and expres sion of the three receptors and four ligands was confirmed by immunocytoche mical staining of the cultured cells. Immunohistochemical analysis of resin - or paraffin-embedded sections from surgical specimens of bronchial mucosa revealed strong membrane staining for EGFR within the bronchial epithelium ; this was particularly evident between basal cells and the basal aspect of columnar cells. The patterns of staining for c-erbB2 and c-erbB3 in the br onchial epithelium were similar to those for EGFR. Immunostaining for EGF, TGF-alpha, AR, HB-EGF, and betacellulin (BTC) was intense in the submucosal glands; with the exception of ETC, EGFR ligand immunoreactivity was also o bserved in the bronchial epithelium, where it paralleled EGFR staining. Col ocalization of c-erbB receptors and ligands demonstrates the potential for productive c-erbB receptor interactions in bronchial epithelium. Further st udy of these interactions may help to define their role in maintenance and repair of the bronchial epithelium.