Pulmonary neuroendocrine cells and neuroepithelial bodies in sudden infant death syndrome: potential markers of airway chemoreceptor dysfunction.
Pulmonary neuroendocrine cells (PNEC), including neuroepithelial bodies (NEB), are amine- and peptide (for example, bombesin)-producing cells that function as hypoxia/hypercapnia-sensitive chemoreceptors that could be involved in the pathophysiology of sudden infant death syndrome (SIDS). We assessed morphometrically the frequency and size of PNEC/NEB in lungs of infants who died of SIDS (n = 21) and compared them to an equal number PNEC/NEB in lungs of age-matched control infants who died of accidental death or homicide, with all cases obtained from the San Diego SIDS/SUDC Research Project database. As a marker for PNEC/NEB we used an antibody against chromogranin A (CGA), and computer-assisted morphometric analysis was employed to determine the relative frequency of PNEC per airway epithelial area (% immunostained area, %IMS), the size of NEB, the number of nuclei/NEB, and the size of the NEB cells. The lungs of SIDS infants showed significantly greater %IMS of airway epithelium (2.72 +/- 0.28 [standard error of the mean, SEM] versus 1.88 +/- 0.24; P < 0.05) and larger NEB (1557 +/- 153 microm(2) versus 1151 +/- 106 microm(2); P < 0.05) compared to control infants. The size of NEB cells was also significantly increased in SIDS cases compared to the controls (180 +/- 6.39 microm(2) versus 157 +/- 8.0 microm(2); P < 0.05), indicating the presence of hypertrophy in addition to hyperplasia. Our findings support previous studies demonstrating hyperplasia of PNEC/NEB in lungs of infants who died of SIDS. These changes could be secondary to chronic hypoxia and/or could be attributable to maturational delay. Morphometric assessment and/or measurement of the secretory products of these cells (for example, CGA, bombesin) could provide a potential biological marker for SIDS.
Cutz
Ernest
E
Division of Pathology, Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, ON, M5G1X8, Canada. ernest.cutz@sickkids.ca
Perrin
Donald G
DG
Pan
Jie
J
Haas
Elisabeth A
EA
Krous
Henry F
HF
D000704:Analysis of Variance; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D002628:Chemoreceptor Cells / Q000378:metabolism / Q000473:pathology*; D053379:Chromogranin A / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D006965:Hyperplasia; D007150:Immunohistochemistry; D007223:Infant; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D008297:Male; D046568:Neuroepithelial Bodies / Q000378:metabolism / Q000473:pathology*; D012189:Retrospective Studies; D013398:Sudden Infant Death / Q000473:pathology*
D015415:Biomarkers; D053379:Chromogranin A