Am. J. Respir. Cell Mol. Biol., Vol 11, No. 2, Aug 1994, 188-198.
Physiologic modulation of bronchial epithelial cell barrier function by polycationic exposure
XY Yu, BH Schofield, T Croxton, N Takahashi, EW Gabrielson and EW Spannhake
Department of Environmental Health Sciences, Johns Hopkins School of Hygiene and Public Health, Baltimore, Maryland 21205.
Bronchial epithelial cells provide a functional barrier to the movement of
water and solutes between the luminal and interstitial compartments of the
lung. Barrier integrity can be compromised by a variety of factors,
including polycationic proteins released by inflammatory cells. We
investigated the characteristics of epithelial barrier function and its
modulation by cationic stimuli in canine bronchial epithelial (CBE) cells
grown in culture. Morphologic characteristics were examined, and barrier
function was assessed by measurements of transepithelial mannitol flux
(flux) and electrical resistance (RT) during a stable, 3- to 14-day culture
period. CBE cultures exhibited progressive mucociliary differentiation and
contained nonciliated, ciliated, and neutral and acidic mucin-secretory
cells. The synthetic polycation, poly-L-lysine (PLL), from 2.5 to 10
micrograms/ml, caused dose-related increases in flux and decreases in RT
that were not accompanied by detectable release of lactate dehydrogenase
(LDH) or changes in histochemical appearance. The effect on RT
spontaneously reversed over a 15-h recovery period. The action of PLL on
flux was not attenuated by treatment of the cells to stabilize cytoskeletal
contractile elements but was immediately attenuated by the addition of
heparin to the challenged cells. These results indicate that modulation of
the barrier integrity of bronchial epithelial cells by cationic proteins,
such as those released by inflammatory cells, represents a physiologic
process that may be regulated by endogenous anionic factors.
