Abstract
The mammalian airways are sensitive to inhaled stimuli, and airway diseases are characterized by hypersensitivity to volatile stimuli, such as perfumes, industrial solvents, and others. However, the identity and function of the cells in the airway that can sense volatile chemicals remain uncertain, particularly in humans. Here, we show that solitary pulmonary neuroendocrine cells (PNECs), which are morphologically distinct and physiologically undefined, might serve as chemosensory cells in human airways. This conclusion is based on our finding that some human PNECs expressed members of the olfactory receptor (OR) family in vivo and in primary cell culture, and are anatomically positioned in the airway epithelium to respond to inhaled volatile chemicals. Furthermore, apical exposure of primary-culture human airway epithelial cells to volatile chemicals decreased levels of serotonin in PNECs, and the led to the release of the neuropeptide calcitonin gene-related peptide (CGRP) to the basal medium. These data suggest that volatile stimulation of PNECs can lead to the secretion of factors that are capable of stimulating the corresponding receptors in the lung epithelium. We also found that the distribution of serotonin and neuropeptide receptors may change in chronic obstructive pulmonary disease, suggesting that increased PNEC-dependent chemoresponsiveness might contribute to the altered sensitivity to volatile stimuli in this disease. Together, these data indicate that human airway epithelia harbor specialized cells that respond to volatile chemical stimuli, and may help to explain clinical observations of odorant-induced airway reactions.