Effect of polycations on the barrier and transport properties of
the alveolar epithelium in situ.
Saumon, Georges, Paul Soler, and Genevi[grave]eve Martet.
INSERM U82, Facult[acute]e Xavier Bichat, Paris, France
APStracts 2:0059L, 1995.
We examined the effect of polycations, classes of which are released
by activated leukocytes, on the transport properties of the alveolar
epithelium in isolated-perfused rat lungs. Protamine, polylysines and
ruthenium red produced rapid, dose-dependent increases in mannitol
permeability (PAMann) when instilled into airspaces. The coupling
between active transepithelial Na+ transport and alveolar fluid
absorption was not altered, despite increases in PAMann of over 10
-fold. The increase in albumin permeability compared to that in
mannitol suggested preservation of alveolar barrier size selectivity.
Tracheal instillation of protamine produced no cellular abnormality
whereas its addition to the perfusate resulted in damage to
endothelial and type I cells. Protamine produced an even larger
(P<0.05) increase in PAMann in the presence of isoproterenol or
dibutyryl cAMP + isobutylmethylxanthine. The stimulation of Na+ and
fluid transport by these agents was unaffected by protamine.
Mastoparan, a peptide that activates G-proteins, produced effects
comparable to those of the polycations. The protamine- and
mastoparan-induced increase in PAMann was abolished by barium, a K+
channel blocker but not by zinc, a membrane-protective cation. Other
K+ channel blockers, tetraethylammonium and quinine, had no effect.
Thus, short term apical application of polycations and mastoparan
alter alveolar epithelium paracellular permeability by a non
-cytotoxic mechanism which is inhibited by barium. The resulting
increase in paracellular permeability does not alter fluid absorption
driven by active Na+ transport. Polycations have very different
effects depending on whether they are present on one side or the
other side of the alveolo-capillary barrier.
Received 1 August 1994; accepted in final form 6 April 1995.
APS Manuscript Number L214-4.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 25 April 1995.