Pulmonary Neuroendocrine Cells in SIDS
Ernest Cutz, WILSON CHAN, Donald G. Perrin · Annals of the New York Academy of Sciences · 1988
The system of pulmonary neuroendocnne (PNE) cells consists of arnine-(serotonin) and peptide-(bombesin, calcitonin, leu-enkephalin) containing cells distributed as single cells and as innervated clusters (neuroepithelial bodies, NEB).'-'While single PNE cells are scattered throughout the epithelium of the tracheobronchial tree, NEB are localized mainly within the epithelium of intrapulmonary airways.'The precise role and function of these cells and their amine and peptide mediators is presently unknown.Experimental studies in neonatal rabbits have shown increased exocytosis of dense core granules (site of arnine and peptide storage) from NEB cells in response to acute h y p ~x i a .~. ~Other recent studies suggest that this response is mediated by vagal inner~ation.~Furthermore, hyperplasia of PNE cells and NEB has been documented in animals exposed to chronic hypoxia.6It has been suggested that NEB may represent airway chemoreceptors (analogous to carotid bodies) involved in autonomic regulation of breathing.Since NEB are prominent in fetalheonatal lungs and decline with postnatal age, this role may be particularly important during neonatal respiratory adaptation.'In this study we have investigated the immunohistochemical profile, distribution, and frequency of PNE cells and NEB in lungs of infants who died of SIDS (n=7, 1.5-5 months of age, mean 3.3 months) and compared them with age-matched controls (previously healthy infants who suffered sudden death; n = 5, 2.5-6 months of age, mean 4.5 months).The lung tissue was fixed in formalin, and deparaffinized sections (after trypsinization) were immunostained with monoclonal antibodies against bombesin, calcitonin (Hybritech, U.S.A.), serotonin, and leu-enkephalin (Sera Lab, U.K.).For quantitative assessment of PNE cells and NEB in lungs of SIDS and control infants, random sections (3-5 per case), immunostained for bombesin, were analyzed.To determine the frequency of bombesin-immunoreactive (BI) cells in airways, areas of airway epithelium and immunoreactive epithelium were outlined on paper using a projecting microscope.The surface areas were measured by an IBAS image analyzer and expressed as percent immunoreactive epithelium (W IRA).An average of 40 airways per T h i s work was supported by grants from NICHD (1 RO1 HD22713-01) and the Medical Research q