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.