Neuroepithelial Bodies In Lungs Research Articles

Immunohistochemical characterization of the chemosensory pulmonary neuroepithelial bodies in the naked mole-rat reveals a unique adaptive phenotype.

The pulmonary neuroepithelial bodies (NEBs) constitute polymodal airway chemosensors for monitoring and signaling ambient gas concentrations (pO2, pCO2/H+) via complex innervation to the brain stem controlling breathing. NEBs produce the bioactive amine, serotonin (5-HT), and a variety of peptides with multiple effects on lung physiology and other organ systems. NEBs in mammals appear prominent and numerous during fetal and neonatal periods, and decline in the post-natal period suggesting an important role during perinatal adaptation. The naked mole-rat (NMR), Heterocephalus glaber, has adapted to the extreme environmental conditions of living in subterranean burrows in large colonies (up to 300 colony mates). The crowded, unventilated burrows are environments of severe hypoxia and hypercapnia. However, NMRs adjust readily to above ground conditions. The chemosensory NEBs of this species were characterized and compared to those of the conventional Wistar rat (WR) to identify similarities and differences that could explain the NMR’s adaptability to environments. A multilabel immunohistochemical analysis combined with confocal microscopy revealed that the expression patterns of amine, peptide, neuroendocrine, innervation markers and chemosensor component proteins in NEBs of NMR were similar to that of WR. However, we found the following differences: 1) NEBs in both neonatal and adult NMR lungs were significantly larger and more numerous as compared to WR; 2) NEBs in NMR had a more variable compact cell organization and exhibited significant differences in the expression of adhesion proteins; 3) NMR NEBs showed a significantly greater ratio of 5-HT positive cells with an abundance of 5-HT; 4) NEBs in NMR expressed the proliferating cell nuclear antigen (PCNA) and the neurogenic gene (MASH1) indicating active proliferation and a state of persistent differentiation. Taken together our findings suggest that NEBs in lungs of NMR are in a hyperactive, functional and developmental state, reminiscent of a persistent fetal state that extends postnatally.

Studies on glomus cell sensitivity to hypoxia in carotid body slices.

Oxygen sensing is a fundamental biological process present in almost all life forms (for reviews see Bunn and Poyton, 1996; Lopez-Barneo et al., 2001). In mammals, the survival in acute hypoxia requires fast respiratory and cardiocirculatory adjustments to ensure sufficient O2 supply to the most critical organs such as the brain or the heart. The main O2 sensor mediating the acute responses to hypoxia is the carotid body (CB), a minute bilateral organ at the bifurcation of the carotid artery innervated by afferent chemosensory fibers. In conditions of hypoxemia, the CBs stimulate the brainstem respiratory centers to evoke hyperventilation. Glomus, or type I, cells are electrically excitable (Duchen et al., 1988, Lopez-Barneo et al., 1988) and constitute the major O2sensitive elements of the CB (Lopez-Barneo et al., 1988, Delpiano and Hescheler, 1989; Peers 1990; Stea and Nurse, 1991, Buckler, 1997). It is broadly accepted that hypoxia signaling in these cells requires the inhibition of O2- sensitive potassium channels of the plasma membrane, which leads to depolarization, external Ca2+influx, and release of the transmitters that activate the afferent sensory fibers (Lopez- Barneo et al., 1993; Urena et al., 1994; Buckler and Vaughan-Jones, 1994; Carpenter et al., 2000; Pardal et al., 2000). This basic scheme of chemotransduction has also been proposed to operate in other 02-sensitive neurosecretory systems, such as cells in the lung neuroepithelial bodies (Youngson et al., 1993), chromaffin cells of the adrenal medulla (Thompson and Nurse, 1998), or PC-12 cells (Zhu et al., 1996).

Increased numbers of neuroepithelial bodies (NEB) in lungs of fetal rhesus monkeys following maternal dexamethasone treatment.

Numbers of neuroepithelial bodies in the lungs of fetal Rhesus monkeys increase in a dose-dependent manner when mothers are treated antenatally with dexamethasone. Maternal doses of 15 mg/kg result in numbers of neuroepithelial bodies in lungs of fetuses of 135-day gestational age not different from those of the mature control group at 162 days. Controls at 135 days are significantly different from those at 162 days. Serotonin immunoreactive neuroepithelial bodies were localized by immunocytochemistry.

Quantitation of pulmonary neuroepithelial bodies in pre- and postnatal rabbits.

The size, density and total number of neuroepithelial bodies (NEB) in the lungs of late fetal, neonatal, and mature rabbits were determined using fluorescence microscopy. In this study lungs from 27-, 29-, 30-, and 31-day fetuses; neonates of ages 2, 7, and 30 days; and 4- and 7(+)-month-old rabbits, were used. The total number of NEB in the entire lung of rabbits from each age group was estimated based on measurements of collapsed lung volume, average NEB diameter, and NEB density (number/mm2). Average NEB diameter increased between 27 and 29 days gestation, then remained constant at 42-44 micron between 29 days gestation and two days postpartum. Thereafter the diameter was significantly reduced in the 7-day group (33.7 micron) and further reduced in the 4-month group (20.3 micron). NEB density was initially high in 27-day fetuses (3.87/mm2), decreased significantly by 30 days gestation, increased to a high level by 2 days postpartum, then fell steadily, reaching the lowest level in the adult (0.15/mm2). This steady decrease in density was paralleled by a large increase in lung volume. The estimated total number of NEB in the lung was constant in all age groups except for a significant drop at 30 and 31 days gestation. These data indicate that the total number of NEB is maintained into adulthood; however, the density and average diameter of NEB decreases rapidly after 2 days postpartum. A sharp decrease in both total number and density observed under fluorescence microscopy at 30 and 31 days gestation suggests a change in NEB cellular activity just prior to birth.

Pulmonary neuro-epithelial bodies—ultrastructure, surface morphology and effects of pharmaca in vitro

Recently, intraepithelial innervated corpuscles, referred to as neuro-epithelial bodies (NEB) have been identified within the airway mucosa of human and animal lungs. The specialized cells of NEB share certain features of APUD (Amine Precursor Uptake and Decarboxylation) endocrine cells, such as argyrophilia, amine contents and presence of cytoplasmic dense core vesicles (DCV). Although the precise function of NEB in lung remains still unknown, it has been suggested that NEB may represent intrapulmonary receptors or alternatively may have an endocrine function.In this study, NEB in lungs of near-term rabbit fetuses (29 days gestation) were examined by transmission (TEM) and scanning electron microscopy (SEM), prior to and following short term organ culture. The ultrastructure and surface morphology of NEB in control animals was compared with a) NEB in rabbit fetal lung explants maintained in vitro for 7-10 days; b) lung explants incubated with reserpine, (an amine releasing agent) or Ca++ ionophore A-23186 (compound used for studies of calcium mediated secretion).