EXPRESSION AND ACTIVITY OF EPIDERMAL GROWTH-FACTOR RECEPTOR IN LATE FETAL-RAT LUNG IS CELL-SPECIFIC AND SEX-SPECIFIC

Epidermal growth factor (EGP) augments late fetal lung maturation by a dvancing the ontogeny of fetal lung development and by stimulating sur factant synthesis. Previous studies have indicated that fibroblast-alv eolar epithelial cell communications mediate surfactant synthesis in t he fetal lung and EGF acts through such a mechanism. We investigated t he hypothesis that differential activity and expression of the epiderm al growth factor receptor (EGF-R) in fetal lung fibroblasts during the canalicular stage of lung development mediates EGF effects. To test t his hypothesis, we examined fetal rat lung fibroblasts (FLFs) and type II cells of late gestation (canalicular and saccular stages; 17-22 da ys) by EGF-R binding techniques, SDS-PAGE, and Western blot analysis. Specific EGF binding increased 181% in day 18 female FLFs, with male F LFs exhibiting a similar increase on day 19. In contrast, specific EGF binding was low in type II cells, did not increase during late gestat ion, and there were no sex-specific differences. SDS-PAGE and Western blot analysis revealed a predominant 170-kDa EGF-R band in fibroblasts that increased with gestation (peak = 19 days), and was stronger in f emales. Immunoprecipitation of EC;F-treated cells demonstrated the tyr osine kinase activity of the identified receptor. In contrast, type II cells showed minimal signal that did not increase until day 21 of ges tation. We also examined whole fetal lung sections by immunohistochemi stry to determine cell-specific expression of the EGF-R in vivo. Immun ohistochemistry revealed specific EGF-R staining in columnar and cuboi dal epithelia of small conducting airways and in mesenchyme of epithel ial-mesenchymal borders (including subepithelial mesenchyme). In contr ast, alveolar epithelia showed minimal staining, while subalveolar mes enchyme EGF-R staining peaked at day 19 of gestation. We conclude that cell-specific and sex-specific differences in EGF-R binding and EGF-R immunolocalization appears in the fetal lung at a developmental stage that is critical for alveolar epithelial cell differentiation. The re sults suggest a role for EGF-R activation in late fetal alveolar epith elial cell maturation, which is mediated through mesenchymal-epithelia l cell communication. (C) 1998 Academic Press.