Jh. Sisson et al., SMOKE AND VIRAL-INFECTION CAUSE CILIA LOSS DETECTABLE BY BRONCHOALVEOLAR LAVAGE CYTOLOGY AND DYNEIN ELISA, American journal of respiratory and critical care medicine, 149(1), 1994, pp. 205-213
Citations number
20
Categorie Soggetti
Emergency Medicine & Critical Care","Respiratory System
The purpose of this study was to quantitate cilia loss following airwa
y epithelial cell injury. Two models of airway injury were used: (1) E
x vivo acute cigarette smoke exposure model: Bovine lungs, obtained di
rectly after slaughter, were ventilated with air or cigarette smoke fo
r 5 min followed immediately by bronchoalveolar lavage (BAL). The bron
chi were examined histologically and bronchial and alveolar fractions
of BAL fluid were examined for cell counts, cell differentials, and ci
lia dynein concentrations using a specific 13S dynein ELISA. Smoke exp
osure resulted in a marked loss of ciliated cells from the bronchial l
uminal surface (2,364 +/- 351 versus 11,090 +/- 542 ciliated cells/mm(
2); p = 0.0001), a comparable increase in ciliated cells in the bronch
ial BAL fraction (0.90 x 10(6) cells/mm(3) versus 0.15 x 10(6) cells/m
m(3); p = 0.0003) and a significant increase in bronchial fluid dynein
concentrations (24.5 +/- 6.0 mu g/ml versus 8.9 +/- 2.2 mu g/ml; p =
0.03) compared with that in air-exposed lungs. The dynein concentratio
ns strongly correlated with the absolute number of ciliated cells reco
vered in the bronchial lavage (r = 0.80; p < 0.0001). (2) In vivo vira
l 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 i
noculation, airway exfoliation of ciliated cells and squamous metaplas
ia were observed histologically, bronchial ciliated cell counts double
d (0.011 +/- 0.003 x 10(6) cells/mm(3) versus 0.026 +/- 0.006 x 10(8)
cells/mm(3); p = 0.002) and bronchial dynein concentrations increased
threefold (2.2 +/- 1.0 mu g/ml versus 7.2 +/- 1.9 mu g/ml; p = 0.02).
The dynein concentrations in this model also correlated with the absol
ute number of ciliated cells recovered in the bronchial lavage (r = 0.
46; p < 0.05). These studies demonstrated that significant ciliated ce
ll loss occurs ex vivo after a very brief exposure to smoke and in viv
o following BRSV infection. In addition, these findings suggest that t
he presence of intraluminal cilia-derived proteins may serve as a usef
ul marker of injury to ciliated epithelium.