Oxygen Sensing in Pulmonary Neuroepithelial Bodies and Related Tumor Cell Model

Abstract

Innervated clusters of amine-and peptide-containing cells widely distributed within the airway epithelium of mammalian lungs, termed neuroepithelial bodies (NEB), were described over 30 years ago (1). Although much progress has been made since then in defining the structural aspects of NEB, their precise function remains unknown. The idea that NEB may represent airway sensors monitoring changes in airway gas concentration has been proposed by early neuroanatomists (2). The first experimental evidence indicating that NEB may indeed represent hypoxia-sensitive airway chemoreceptors has been reported by Lauweryns et al. (3,4). However, the underlying mechanisms and the effects on lung function remained undefined. Further advances in characterizing functional aspects of NEB cells have occurred with development of suitable in vitro models to overcome the problem of their small numbers and widespread distribution within anatomically complex lung parenchyma (5,6). Using cultures of NEB cells isolated from near-term fetal rabbit lungs, amine (serotonin, 5-HT) release was observed after exposure to different levels of hypoxia confirming their intrinsic O2 sensitivity (6). The same model was subsequently used for electrophysiological characterization of ionic currents and the O2-sensing mechanism (7). These latter studies have strengthened the view that NEB represent airway O2 sensors analogous to carotid body (CB) glomus cells, well-defined arterial chemoreceptors (8). Development of additional experimental models, such as fresh lung slice preparations, has allowed direct electrophysiological recordings from NEB cells in their natural environment (9). The identification of O2sensing properties in small-cell lung carcinoma (SCLC) cell line H-146, a tumor counterpart of NEB in normal lungs, has been instrumental in studies of molecular mechanism involved in O2 sensitivity (10). There is also new information provided by anatomical studies on the distribution and innervation of NEB (11). The principal aim of this chapter is to review recent progress in the cell and molecular biology of NEB usingvarious experimental models and approaches, focusing on their potential role as airway chemoreceptors.