title: Smoke and viral infection cause cilia loss detectable by bronchoalveolar lavage cytology and dynein ELISA.
abstract: 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 10(6) cells/mm3 versus 0.15 x 10(6) cells/mm3; p = 0.0003) and a significant increase in bronchial fluid dynein concentrations (24.5 +/- 6.0 micrograms/ml versus 8.9 +/- 2.2 micrograms/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 10(6) cells/mm3 versus 0.026 +/- 0.006 x 10(6) cells/mm3; p = 0.002) and bronchial dynein concentrations increased threefold (2.2 +/- 1.0 micrograms/ml versus 7.2 +/- 1.9 micrograms/ml; p = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Medicine, University of Nebraska Medical Center, Omaha 68198-5300.
authors.forename: J H
authors.initials: JH
authors.lastname: Sisson
authors.forename: A
authors.initials: A
authors.lastname: Papi
authors.forename: J D
authors.initials: JD
authors.lastname: Beckmann
authors.forename: K L
authors.initials: KL
authors.lastname: Leise
authors.forename: J
authors.initials: J
authors.lastname: Wisecarver
authors.forename: B W
authors.initials: BW
authors.lastname: Brodersen
authors.forename: C L
authors.initials: CL
authors.lastname: Kelling
authors.forename: J R
authors.initials: JR
authors.lastname: Spurzem
authors.forename: S I
authors.initials: SI
authors.lastname: Rennard
mesh_terms: D000818:Animals; D001706:Biopsy; D015153:Blotting, Western; D001980:Bronchi / Q000737:chemistry* / Q000473:pathology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry* / Q000166:cytology*; D001999:Bronchoscopy; D002417:Cattle; D002452:Cell Count; D002923:Cilia / Q000737:chemistry / Q000473:pathology; D004195:Disease Models, Animal; D004398:Dyneins / Q000032:analysis*; D004797:Enzyme-Linked Immunosorbent Assay; D016014:Linear Models; D008679:Metaplasia; D018357:Respiratory Syncytial Virus Infections / Q000473:pathology*; D018112:Respiratory Syncytial Virus, Bovine; D012907:Smoking / Q000473:pathology*
chemical_list: D004398:Dyneins