Solitary neuroendocrine cells and neuroepithelial bodies in the lower airways of embryonic, fetal, and postnatal sheep

Abstract

The sheep pulmonary intraepithelial APUD system was studied by histochemical, immunocytochemical, and electron microscopy techniques during different periods of lung development: embryonic, fetal (pseudoglandular, canalicular, and alveolar), and postnatal. The cells of the ovine pulmonary intraepithelial APUD system were found randomly distributed throughout the conducting and respiratory or undifferentiated airways. They appeared as isolated cells (solitary neuroendocrine cells) or in groups (neuroepithelial bodies). These cells were argyrophilic and immunoreactive for neuron-specific enolase but were not argentaffin. Ultrastructurally they were characterized by a basal position in the respiratory epithelium and by the presence of neurosecretory granules (dense-core vesicles) ranging between 65 and 230 nm of diametre. Quantitative studies showed that single neuroendocrine cells were more numerous in distal conducting airways and at fetal stages. The earliest identifiable argyrophilic and NSE-immunoreactive neuroendocrine cells in sheep airways appeared at gestational week 5, close to the term of the embryonic period.

Quantitative Study of Pulmonary Endocrine Cells in Fetal, Postnatal and Adult Sheep

“…by light microscopic immunohistochemistry [5][6][7]. To the best of our knowledge, so far only a few studies have analyzed the intraepithelial endocrine cells during the different developmental stages of lung in the fetal sheep lower respiratory tract [8]. However, the agerelated changes of pulmonary endocrine cells of sheep from fetal period to adult are still not well known.…”

“…Therefore, our present study is the first to document precisely the developmental course of pulmonary endocrine cells in sheep lungs by the immunohistochemical quantitative analysis. Recent immunohistochemical studies of various kind of mammals showed that the pulmonary endocrine cells have various kinds of neuroendocrine markers such as serotonin [1,9,11,12,18,21,28], bombesin [1,6,12,23,24,28], gastrin-releasing peptide [1], cholecystokinin [27], calcitonin [1,12,23], calcitonin gene related peptide [1,28], leuenkephalin [1,12], NSE [1,8,18] and chromogranin [1].…”

“…These immunohistochemical studies revealed that serotonin, cholecystokinin and neuron-specific enolase (NSE) immunoreactivity were identified in both solitary endocrine cells and endocrine cell clusters (i.e., neuroepithelial bodies, NEBs) of the sheep lung. Balaguer et al [8,9] also showed that the earliest identifiable endocrine cells appeared at 5 weeks of gestation, which is close to the term of the embryonic period. They also reported that endocrine cells in the sheep airways were more numerous in distal conducting airways and fetal stages.…”

“…Pulmonary endocrine cells are widely distributed throughout the airway mucosa and are thought to play an important role in lung development and maturation from intrauterine life to the postnatal period [1,6,8,9,11,16,18,27]. The principal role of pulmonary endocrine cells during intrauterine life is considered to involve the maintenance of active pulmonary vasoconstriction in the relatively hypoxic lung, as well as the rapid vasodilation upon the aeration of the lung at birth [12].…”

“…Since then, several reports have been published on the structure and distribution of pulmonary endocrine cells of sheep [8][9][10]28]. These immunohistochemical studies revealed that serotonin, cholecystokinin and neuron-specific enolase (NSE) immunoreactivity were identified in both solitary endocrine cells and endocrine cell clusters (i.e., neuroepithelial bodies, NEBs) of the sheep lung.…”