DEVELOPMENT OF CELL SPECIFIC EPIDERMAL GROWTH FACTOR (EGF) BINDING IN FETAL RAT LUNG

Abstract

EGF regulates fetal lung type II cell differentiation by advancing the developmental window under which fibroblast-type II cell communications occur. EGF acts by binding to its specific receptor, but the ontogeny of EGF receptor binding by specific lung cells is unknown. We hypothesized that EGF binding would exhibit developmental changes in the fetal lung fibroblast but not the type II cell, consistent with the primary role of the fibroblast in directing development of alveolar cells, and that these changes would occur earlier in the female fetal lung fibroblast, consistent with the earlier effect of EGF on female fibroblast-type II cell interactions. Day 17, 18, and 19 (term - 22 days) sex-specific fetal rat lung fibroblasts and type II cells were grown to confluence. Specific EGF binding was measured using 0.40 ng/ml 125I EGF and a 500 fold excess of unlabelled EGF. Specific binding in day 17 female fibroblasts was twice that of day 17 male fibroblasts (102 ± 11 vs. 51 ± 10 cpm/nmol DNA; mean ± SEM, n-3). Specific binding doubled on day 18, maintaining the female-male difference. On day 19 binding levels were similar (females: 248 ± 69; males: 233 ± 78 cpm/nmol DNA, mean ± SEM, n=4). In contrast, specific binding in type II cells remained approximately 50 cpm/nmol DNA at all days, with no sex-specific differences. We conclude that cell-specific and sex-specific changes in EGF binding appear in the fetal lung at a developmental stage critical for type II cell differentiation. This is consistent with the effect that EGF has on the fibroblast in advancing fibroblast-type II cell communications.