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. [ψLeu¹³, Leu¹⁴] BN(1–14), a BN antagonist, blocked the stimulation induced by BN. [D‐Cpa⁶, ψLeu¹³,Phe¹⁴] BN(6–14), a mixed agonist‐antagonist, showed partial agonist activity in HBE cells. [D‐Phe¹, Leu^8,9] 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. Analogs to BN or GRP may have potential in modulating responses to neuropeptides in the human lung. © 1993 Wiley‐Liss, Inc.