Despite many recent studies, the control of neonatal pulmonary vascular and airway resistance remains poorly understood. Recently, two additional intrapulmonary control systems, pulmonaary neuroendocrine cells (PNEC) and the pulmonary peptidergic innervation (PPI), have been describe, both of which may influence pulmonary vascular and airway tone in the neonate. PNEC are granulated cells that line the airways of fetal, neonatal, and adult lungs. THey are particularly numerous in the neonatal period and contain peptides (bombesin, calcitonin, leu-enkephalin) amines (serotonin) known to affect smooth muscle tone in other organ systems. The PPI, composed association with pulmonary airways and vessels of all sizes. Both these peptides are known to profoundly influence smooth muscle tone in other organ systems. Limited indirect anatomic and physiologic evidence has suggested a role for both systems in altering intrapulmonary smooth muscle tone, particulary in neonates; however, basic knowledge of both systems is extremely limited.
The aim of this research program is to provide the fundamental knowledge necessary to assess the role of both these systems in influencing neonatal pulmonary vascular and airway tone under normal and pathologic conditions.
This aim will be accomplished in the following fashion: Structure: (a) Determination of the development and distribution of PNEC and PPI within the lung using immunohistochemical techniques. (b) Determination of the anatomic distribution of receptors for the above peptides and amines, and their relationship to receptors for the presently characterized intrapulmonary control mechanisms (adrenergic and cholinergic innervation) using radioautography. (c) Determination of pathologic alterations in the structure and distribution of PNEC, PPI and adrenergic, cholinergic, and peptidergic receptors in acute and chronic neonatal cardiopulmonary disease where alterations in vascular and airway tone are either known to play a significant role (hyaline membrane disease, bronchopulmonary dysplasia, congenital heart disease) or may play a dignificant role (sudden infant death syndrome, cystic fibrosis). Function: (a) Assessment of the direct effects of peptides and amines released by pulmonary neuroendocrine cells and the pulmonary peptidergic innervation on vascular and airway smooth muscle tone using a well-characterized neonatal lamb model of pulmonary vascular and airway resistance. Should these two systems, pulmonary neuroendocrine cells and the pulmonary peptidergic innervation, influence neonatal vascular airway tone; understanding their normal function and their alterations in common neonatal cardiopulmonary pathologic states may lead to novel therapies for a number of currently untreatable, or poorly treatable, neonatal cardiopulmonary diseases.
| Johnson, D E; Wobken, J D; Landrum, B G (1988) Changes in bombesin, calcitonin, and serotonin immunoreactive pulmonary neuroendocrine cells in cystic fibrosis and after prolonged mechanical ventilation. Am Rev Respir Dis 137:123-31 |
| Gatto, C; Green, T P; Johnson, M G et al. (1987) Localization of quantitative changes in pulmonary beta-receptors in ovalbumin-sensitized guinea pigs. Am Rev Respir Dis 136:150-4 |
| Johnson, D E; Wobken, J D (1987) Calcitonin gene-related peptide immunoreactivity in airway epithelial cells of the human fetus and infant. Cell Tissue Res 250:579-83 |
