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Publication : Initiation and maturation of cilia-generated flow in newborn and postnatal mouse airway.

First Author  Francis RJ Year  2009
Journal  Am J Physiol Lung Cell Mol Physiol Volume  296
Issue  6 Pages  L1067-75
PubMed ID  19346437 Mgi Jnum  J:164972
Mgi Id  MGI:4835840 Doi  10.1152/ajplung.00001.2009
Citation  Francis RJ, et al. (2009) Initiation and maturation of cilia-generated flow in newborn and postnatal mouse airway. Am J Physiol Lung Cell Mol Physiol 296(6):L1067-75
abstractText  Mucociliary clearance in the adult trachea is well characterized, but there are limited data in newborns. Cilia-generated flow was quantified across longitudinal sections of mouse trachea from birth through postnatal day (PND) 28 by tracking fluorescent microsphere speed and directionality. The percentage of ciliated tracheal epithelial cells, as determined by immunohistochemistry, was shown to increase linearly between PND 0 and PND 21 (R(2) = 0.94). While directionality measurements detected patches of flow starting at PND 3, uniform flow across the epithelia was not observed until PND 7 at a approximately 35% ciliated cell density. Flow became established at a maximal rate at PND 9 and beyond. A linear correlation was observed between the percentage of ciliated cells versus flow speed (R(2) = 0.495) and directionality (R(2) = 0.975) between PND 0 and PND 9. Cilia beat frequency (CBF) was higher at PND 0 than at all subsequent time points, but cilia beat waveform was not noticeably different. Tracheal epithelia from a mouse model of primary ciliary dyskinesia (PCD) harboring a Mdnah5 mutation showed that ciliated cell density was unaffected, but no cilia-generated flow was detected. Cilia in mutant airways were either immotile or with slow dyssynchronous beat and abnormal ciliary waveform. Overall, our studies showed that the initiation of cilia-generated flow is directly correlated with an increase in epithelial ciliation, with the measurement of directionality being more sensitive than speed for detecting flow. The higher CBF observed in newborn epithelia suggests unique physiology in the newborn trachea, indicating possible clinical relevance to the pathophysiology of respiratory distress seen in newborn PCD patients.
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