title: Effect of polycations on barrier and transport properties of alveolar epithelium in situ.
abstract: 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.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U82, Faculté Xavier Bichat, Paris, France.
authors.forename: G
authors.initials: G
authors.lastname: Saumon
authors.forename: P
authors.initials: P
authors.lastname: Soler
authors.forename: G
authors.initials: G
authors.lastname: Martet
mesh_terms: D000042:Absorption; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001826:Body Fluids / Q000378:metabolism; D002412:Cations / Q000494:pharmacology*; D000242:Cyclic AMP / Q000494:pharmacology; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins; D008353:Mannitol / Q000493:pharmacokinetics; D010455:Peptides; D010539:Permeability / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000493:pharmacokinetics; D014862:Wasp Venoms / Q000494:pharmacology
chemical_list: D000318:Adrenergic beta-Agonists; D002412:Cations; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D015221:Potassium Channels; D014862:Wasp Venoms; D008353:Mannitol; C037500:mastoparan; D012964:Sodium; D000242:Cyclic AMP