Effects of bombesin and gastrin-releasing peptide on human bronchial epithelial cells from a series of donors: individual variation and modulation by bombesin analogs

Human pulmonary neuroendocrine cells produce a variety of Hormones, including mammalian bombesin (BN) or gastrin-releasing peptide (GRP). Neuroendocrine cell hyperplasia and increased release of BN-like Peptides occur in several diseases of the airways, including chronic obstructive pulmonary disease (COPD) and bronchopulmonary dysplasia. Growth stimulation of human bronchial epithelial cells by BN, as measured in a colony-forming assay, has been reported previously (Willey et al.:Exp. Cell Res. 153:245-248, 1984). In a follow-up to this report, we examined the response of human bronchial epithelial (HBE) cells to BN or GRP in a similar system, using cells derived from 13 human tissue donors. A stimulatory response (increased colony-forming efficiency) was found in cultures from 8 donors, including 3 with COPD. Statistical significance was found for the data from 5 of these 8 donors. The other 5 donors, 1 normal and 4 lung Cancer patients, showed inhibition of colony formation by BN or GRP. Statistical significance was found for 3 of these donors. The ability of BN analogs to modulate BN stimulation was examined in cells from a donor with COPD. [psi Leu13,Leu14] BN(1-14), a BN antagonist, blocked the stimulation induced by BN. [D-Cpa6,psi Leu13,Phe14] BN(6-14), a mixed agonist-antagonist, showed partial agonist activity in HBE cells. [D-Phe1,Leu8,9] Litorin, an agonist, also showed agonist activity in a colony-forming assay with cells from these donors. These results indicate that responsiveness to BN/GRP may vary widely in the human population. Responsiveness may be heightened in disease states involving a proliferation of neuroendocrine cells.(ABSTRACT TRUNCATED AT 250 WORDS)