The Journal of clinical investigation
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Cigarette smoking is associated with hyperplasia of pulmonary neuroendocrine cells and variably increased levels of bombesin-like peptides in the lower respiratory tract. Because the neuropeptide bombesin is a chemoattractant for monocytes and a mitogen for 3T3 fibroblasts, we hypothesized that an excess of neuroendocrine cells and bombesin-like peptides could contribute to lung inflammation and fibrosis in certain cigarette smokers. Eosinophilic granuloma is a fibrotic lung disease of unknown etiology that in adults occurs almost invariably in cigarette smokers. ⋯ The patients with eosinophilic granuloma exhibited a 10-fold increase in neuroendocrine cells with bombesin-like immunoreactivity compared to both smokers (P = 0.005) and patients with idiopathic pulmonary fibrosis (P = 0.005). In addition, bombesin produced a significant mitogenic effect on cultured human adult lung fibroblasts at concentrations of 1 nM and above. We conclude that increased numbers of pulmonary neuroendocrine cells with bombesin-like immunoreactivity are commonly found in patients with eosinophilic granuloma and, since bombesin-like peptides are chemotactic for monocytes and mitogenic for human lung fibroblasts, we speculate that neuroendocrine cell hyperplasia may be important in the pathogenesis of eosinophilic granuloma in adult cigarette smokers.