The pulmonary NEC system
The pulmonary NEC system consists of solitary cells and distinctive
clusters of these cells, termed neuroepithelial bodies (NEB), localized
in the airway epithelium 3. Pulmonary NEC express a
variety of bioactive substances, including amines (serotonin and 5-HT)
and neuropeptides (calcitonin gene-related peptide, gamma-aminobutyric
acid, vasoactive intestinal polypeptide and bombesin). Pulmonary NEC/NEB
are found in all fetal stages, at which time they are intimately
involved in the regulation of lung development 3,9,15.
In fetal life, physiological hypoxia and mechanical stretch caused by
fluid dynamics in the airway lumen upregulate pulmonary NEC functions,
promoting epithelial cell proliferation, branching morphogenesis and
type-II pneumocytes differentiation15.
Mechanical-stretch-induced 5-HT release from NEC is mediated by
mechanosensitive channels, independent of the exocytic pathway. In
contrast, hypoxia-induced secretion of 5-HT and of neuropeptides occurs
principally via classical exocytosis of dense core vesicles, a process
mediated by voltage activated Ca++ channels without
apparent involvement of mechanosensitive channels 3.
After birth, pulmonary NEC decrease and often disappear with lung
maturation by 1-2 years of age 15. This may not be the
case in conditions of pathology, such as pediatric PH, BPD, SIDS, CCHS
and CF 3,15-18. Acute or persistent hypoxia and injury
to the airways, features of some of these disorders, are recognized
stimuli that can activate pulmonary NEC inducing release of bioactive
neuropeptides, such as bombesin, which can modulate lung damage, as
shown in premature infants with BPD, or trigger smooth muscle
contraction, as shown in NEHI 3,9,15-18. In this
latter disorder, a predominant abundance of pulmonary bombesin-positive
NEC in small airways and distal bronchiole has been described as the
characteristic finding 18-20. A bombesin-induced
airflow limitation at that level is consistent with the clinical
presentation, i.e. small airway obstruction and
air-trapping7,18.