P M Bummer1, S Aziz, M N Gillespie. 1. Division of Medicinal Chemistry and Pharmaceutics, College of Pharmacy, University of Kentucky, Lexington 40536-0082, USA.
Abstract
PURPOSE: The purpose of this study is to investigate the interaction of cationic polyamino acids, polylysine and polyarginine, with rat pulmonary surfactant at the air/water interface. METHODS: Surface pressure measurements of rat pulmonary surfactant in the presence and absence of polyamino acids were carried out in both dynamic and static modes. RESULTS: In dynamic cycle studies, compression and expansion of adsorbed surfactant films in the presence of the cationic polyamino acids resulted in a delayed attainment of the plateau surface pressure. In area studies of spread surfactant films at constant surface pressure, cationic polyamino acids in the subphase resulted in an increase in film area. Increased film area was also observed when a polyamino acid was injected beneath films of dipalmitoyl-phosphatidylcholine/phosphatidylglycerol. In the presence of the cationic polyamino acids, the equilibrium surface pressure (at constant film area) of pulmonary surfactant was elevated in a concentration- and molecular weight-dependent manner. CONCLUSIONS: These data indicate that the model cationic peptides interact with surfactant lipid, possibly electrostatically with phosphatidylglycerol. It is concluded that the surface activity of pulmonary surfactant is significantly inhibited by the presence of the polycations, possibly by the formation of a mixed lipid/polyamino acid film.
PURPOSE: The purpose of this study is to investigate the interaction of cationic polyamino acids, polylysine and polyarginine, with rat pulmonary surfactant at the air/water interface. METHODS: Surface pressure measurements of rat pulmonary surfactant in the presence and absence of polyamino acids were carried out in both dynamic and static modes. RESULTS: In dynamic cycle studies, compression and expansion of adsorbed surfactant films in the presence of the cationic polyamino acids resulted in a delayed attainment of the plateau surface pressure. In area studies of spread surfactant films at constant surface pressure, cationic polyamino acids in the subphase resulted in an increase in film area. Increased film area was also observed when a polyamino acid was injected beneath films of dipalmitoyl-phosphatidylcholine/phosphatidylglycerol. In the presence of the cationic polyamino acids, the equilibrium surface pressure (at constant film area) of pulmonary surfactant was elevated in a concentration- and molecular weight-dependent manner. CONCLUSIONS: These data indicate that the model cationic peptides interact with surfactant lipid, possibly electrostatically with phosphatidylglycerol. It is concluded that the surface activity of pulmonary surfactant is significantly inhibited by the presence of the polycations, possibly by the formation of a mixed lipid/polyamino acid film.
Authors: P M Bummer; J A Baughn; L P Sanders; K R Absher; W N O'Connor; J W Olson; M N Gillespie Journal: Toxicology Date: 1994-05-31 Impact factor: 4.221