Developmental regulation of SP-A receptor in fetal rat lung

We studied the ontogeny and developmental regulation of the recently isolated SP-A receptor in fetal and postnatal rat lung. Our results show that SP-A receptor protein levels are first detectable at 16-18 days' gestation in fetal rat lung. There is a biphasic change in its levels with an initial marked increase during late gestation, a decrease in the early postnatal period (4-7 days of age), followed by another rise in levels during the second postnatal week. The results of binding isotherms show that maximal binding of monoclonal antibody to the receptor increases with differentiation of the type II cell, indicating that the increase during fetal lung development is due in part to increased numbers of receptors per cell. Bombesin (10 nM-1 microM) enhanced SP-A receptor protein levels threefold in fetal lung explants as early as 6 hours in culture. This effect of bombesin was associated with increased proliferation of type II cells as measured by levels of proliferating cell nuclear antigen (PCNA). We conclude that the increase in SP-A receptor protein level in late gestation fetal rat lung is due to increased numbers of receptors per cell and increased numbers of type II cells. Bombesin may have an important role during lung development by paracrine mechanisms that result in proliferation of lung cells.