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.