TY - JOUR
T1 - Smoke and viral infection cause cilia loss detectable by bronchoalveolar lavage cytology and dynein ELISA
AU - Sisson, Joseph Harold
AU - Papi, Alberto
AU - Beckmann, Joe D.
AU - Leise, Kathryn L.
AU - Wisecarver, James Lowell
AU - Brodersen, Bruce W.
AU - Kelling, Clayton L
AU - Spurzem, John R.
AU - Rennard, Stephen I.
PY - 1994/1
Y1 - 1994/1
N2 - The purpose of this study was to quantitate cilia loss following airway epithelial cell injury. Two models of airway injury were used: (1) Ex vivo acute cigarette smoke exposure model: Bovine lungs, obtained directly after slaughter, were ventilated with air or cigarette smoke for 5 min followed immediately by bronchoalveolar lavage (BAL). The bronchi were examined histologically and bronchial and alveolar fractions of BAL fluid were examined for cell counts, cell differentials, and cilia dynein concentrations using a specific 13S dynein ELISA. Smoke exposure resulted in a marked loss of ciliated cells from the bronchial luminal surface (2,364 ± 351 versus 11,090 ± 542 ciliated cells/mm2; p = 0.0001), a comparable increase in ciliated cells in the bronchial BAL fraction (0.90 x 106 cells/mm3 versus 0.15 x 106 cells/mm3; p = 0.0003) and a significant increase in bronchial fluid dynein concentrations (24.5 ± 6.0 μg/ml versus 8.9 ± 2.2 μg/ml; p = 0.03) compared with that in air-exposed lungs. The dynein concentrations strongly correlated with the absolute number of ciliated cells recovered in the bronchial lavage (r = 0.80; p < 0.0001). (2) In vivo viral infection model: Healthy cattle underwent bronchoscopy 3 days before and 7 days after inoculation with bovine respiratory syncytial virus (BRSV). BAL fluid was examined as in the first model. Following BRSV inoculation, airway exfoliation of ciliated cells and squamous metaplasia were observed histologically, bronchial ciliated cell counts doubled (0.011 ± 0.003 x 106 cells/mm3 versus 0.026 ± 0.006 x 106 cells/mm3; p = 0.002) and bronchial dynein concentrations increased threefold (2.2 ± 1.0 μg/ml versus 7.2 ± 1.9 μg/ml; p = 0.02). The dynein concentrations in this model also correlated with the absolute number of ciliated cells recovered in the bronchial lavage (r = 0.46; p < 0.05). These studies demonstrated that significant ciliated cell loss occurs ex vivo after a very brief exposure to smoke and in vivo following BRSV infection. In addition, these findings suggest that the presence of intraluminal cilia-derived proteins may serve as a useful marker of injury to ciliated epithelium.
AB - The purpose of this study was to quantitate cilia loss following airway epithelial cell injury. Two models of airway injury were used: (1) Ex vivo acute cigarette smoke exposure model: Bovine lungs, obtained directly after slaughter, were ventilated with air or cigarette smoke for 5 min followed immediately by bronchoalveolar lavage (BAL). The bronchi were examined histologically and bronchial and alveolar fractions of BAL fluid were examined for cell counts, cell differentials, and cilia dynein concentrations using a specific 13S dynein ELISA. Smoke exposure resulted in a marked loss of ciliated cells from the bronchial luminal surface (2,364 ± 351 versus 11,090 ± 542 ciliated cells/mm2; p = 0.0001), a comparable increase in ciliated cells in the bronchial BAL fraction (0.90 x 106 cells/mm3 versus 0.15 x 106 cells/mm3; p = 0.0003) and a significant increase in bronchial fluid dynein concentrations (24.5 ± 6.0 μg/ml versus 8.9 ± 2.2 μg/ml; p = 0.03) compared with that in air-exposed lungs. The dynein concentrations strongly correlated with the absolute number of ciliated cells recovered in the bronchial lavage (r = 0.80; p < 0.0001). (2) In vivo viral infection model: Healthy cattle underwent bronchoscopy 3 days before and 7 days after inoculation with bovine respiratory syncytial virus (BRSV). BAL fluid was examined as in the first model. Following BRSV inoculation, airway exfoliation of ciliated cells and squamous metaplasia were observed histologically, bronchial ciliated cell counts doubled (0.011 ± 0.003 x 106 cells/mm3 versus 0.026 ± 0.006 x 106 cells/mm3; p = 0.002) and bronchial dynein concentrations increased threefold (2.2 ± 1.0 μg/ml versus 7.2 ± 1.9 μg/ml; p = 0.02). The dynein concentrations in this model also correlated with the absolute number of ciliated cells recovered in the bronchial lavage (r = 0.46; p < 0.05). These studies demonstrated that significant ciliated cell loss occurs ex vivo after a very brief exposure to smoke and in vivo following BRSV infection. In addition, these findings suggest that the presence of intraluminal cilia-derived proteins may serve as a useful marker of injury to ciliated epithelium.
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U2 - 10.1164/ajrccm.149.1.8111584
DO - 10.1164/ajrccm.149.1.8111584
M3 - Article
C2 - 8111584
AN - SCOPUS:0028014332
SN - 1073-449X
VL - 149
SP - 205
EP - 213
JO - American Journal of Respiratory and Critical Care Medicine
JF - American Journal of Respiratory and Critical Care Medicine
IS - 1
ER -