AJP - Lung Cellular and Molecular Physiology, Vol 269, Issue 2 185-L194, Copyright © 1995 by American Physiological Society
Effect of polycations on barrier and transport properties of alveolar epithelium in situ
G. Saumon, P. Soler and G. Martet
Institut National de la Sante et de la Recherche Medicale U82, Faculte Xavier Bichat, Paris, France.
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 > 10-fold increases in PAmann. The increase in albumin
permeability compared with 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 adenosine 3',5'-cyclic monophosphate +
3-isobutyl-1-methyl-xanthine. 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 noncytotoxic mechanism that 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 alveolar capillary barrier.
