Pulmonary neuroendocrine cells. Their secretory products and their potential roles in health and chronic lung disease in infancy

Pulmonary neuroendocrine cells (PNEC) are granulated epithelial cells distributed throughout conducting airways. Among the bioactive products identified within the secretory granules of these cells are potent mitogens and bronchoactive and vasoactive agents. The secretory status of these cells, which are in greatest number in the fetus and newborn, is modulated by neural reflexes and by changes in airway gas composition. The aggregate data suggest roles for PNEC in airway 'chemoception' and/or regulation of airway epithelial differentiation. Marked increases in PNEC are observed in broncopulmonary dysplasia, where airway and alveolar fibrosis, epithelial metaplasia, and airway and vascular smooth muscle hypertrophy contribute to marked pathophysiologic changes in lung function. Considering the biologic effects of PNEC secretory products, particularly gastrin-releasing peptide on airway epithelial cell and fibroblast proliferation, we propose that an increase in PNEC secretory products in the regenerating airway epithelium may contribute to the development of the pathologic alterations in lung structure seen in bronchopulmonary dysplasia. In this proposed scheme, secretion of abnormally large amounts of bronchoactive and vasoactive agents from PNEC (e.g., serotonin, gastrin-releasing peptide) in response to airway hypoxia and hypercapnia may be partially responsible in the genesis of ractive airway disease and pulmonary hypertension seen in this disease.