Bombesin inhibits apoptosis in developing fetal rat lung

We have shown recently that apoptosis occurs during fetal and postnatal lun g development. Our hypothesis that branching morphogenesis occurs through a delicate balance of cell proliferation and apoptosis predicts that substan ces that enhance branching of the airways would affect both cell proliferat ion and apoptosis in the lung. Bombesin-like peptides have a mitogenic effe ct on bronchial epithelium and fibroblasts, and bombesin has been shown to enhance branching morphogenesis in fetal lung. We used organ cultures of 16 -day gestation fetal rat lung to study the effects of bombesin on apoptosis . Cultures were incubated in serumless medium alone or exposed to 1 mu M bo mbesin for 0-48 h. Levels of apoptosis were quantified using the TUNEL assa y and expressed as percentage of apoptotic cells in paraffin sections of ex plants. Bombesin significantly inhibited apoptosis in fetal lung mesenchyme 48 h in culture by more than 50% (p < 0.05). The effects of bombesin on ap optosis were prevented completely if explants were exposed to the specific bombesin receptor antagonist, [D-Phe(12)]bombesin. To examine if the absenc e of serum in the media could have accounted for some of these effects, exp lants were cultured for 48 h in serumless medium, medium containing 10% fet al bovine serum, serumless medium with 1 mu M bombesin, or medium containin g both 10% fetal bovine serum and 1 mu M bombesin. The addition of fetal bo vine serum to the media reduced apoptosis significantly. The effect of feta l bovine serum on apoptosis was additive with bombesin, We conclude that bo mbesin inhibits apoptosis in developing fetal rat lung mesenchyme through i ts interaction with the bombesin receptor.