Published ahead of print on April 13, 2006, doi:10.1165/rcmb.2005-0468OC
© 2006 American Thoracic Society DOI: 10.1165/rcmb.2005-0468OC Pulmonary Neuroendocrine Cells, Airway Innervation, and Smooth Muscle Are Altered in Cftr Null MiceDivision of Pathology, Department of Paediatric Laboratory Medicine, and The Research Institute, The Hospital for Sick Children; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto; and Animal Care and Veterinary Services, University of Western Ontario, London, Ontario, Canada Correspondence and requests for reprints should be addressed to Herman Yeger, Ph.D., Department of Paediatric Laboratory Medicine, Division of Pathology, 555 University Avenue, The Hospital for Sick Children, Toronto, ON, M5G 1X8 Canada. E-mail: hermie{at}sickkids.ca
The amine- and peptide-producing pulmonary neuroendocrine cells (PNEC) are widely distributed within the airway mucosa of mammalian lung as solitary cells and innervated clusters, neuroepithelial bodies (NEB), which function as airway O2 sensors. These cells express Cftr and hence could play a role in the pathophysiology of cystic fibrosis (CF) lung disease. We performed confocal microscopy and morphometric analysis on lung sections from Cftr–/– (null), Cftr+/+, and Cftr+/– (control) mice at developmental stages E20, P5, P9, and P30 to determine the distribution, frequency, and innervation of PNEC/NEB, innervation and cell mass of airway smooth muscle, and neuromuscular junctions using synaptic vesicle protein 2, smooth muscle actin, and synaptophysin markers, respectively. The mean number of PNEC/NEB in Cftr–/– mice was significantly reduced compared with control mice at E20, whereas comparable or increased numbers were observed postnatally. NEB cells in Cftr null mice showed a significant reduction in intracorpuscular nerve endings compared with control mice, which is consistent with an intrinsic abnormality of the PNEC system. The airways of Cftr–/– mice showed reduced density (
Key Words: autonomic nervous system • CF • Cftr null mice • lung disease This article has been cited by other articles:
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20–30%) of smooth muscle innervation, decreased mean airway smooth muscle mass (
