Effects of Four Components of the Polyene Antibiotic, Filipin, on Phospholipid Spherules (Liposomes) and Erythrocytes

Abstract

Abstract Effects of a complex polyene antibiotic, filipin, and its four components were studied upon biological (erythrocyte) and artificial (liposome) membranes in order to test the hypothesis of polyene action. The hemolytic activity of filipin complex could be removed more effectively by liposomes which had cholesterol incorporated (phosphatidyl choline (7)-dicetylphosphate (2)-cholesterol (1)) than by cholesterol-lacking spherules (phosphatidyl choline (7)-dicetylphosphate (2)-cholesterol (0)). The order of hemolytic activity of filipin components was: filipin II ≅ filipin III >> filipin I g filipin IV and this order paralleled their biological action. Filipin III, which is the major (53%) component of the complex, preferentially disrupted liposomes prepared with cholesterol (judged by release of CrO4=); filipin II (25% of the complex) indiscriminately disrupted liposomes whether or not cholesterol was present. Filipin I and filipin IV were far less disruptive to the artificial structures. Other phospholipids (sphingomyelin g cardiolipin >> phosphatidyl ethanolamine) were also shown to interact with filipin components. The experiments resolve discrepancies reported with filipin complex, the interaction of which with artificial membranes prepared either with or without cholesterol depends upon the relative enrichment of the complex in one or another of its components and the subsequent polyene-lipid ratio. Consequently, although filipins clearly interact with phospholipids in model systems, no significant objections remain to the general sterol receptor hypothesis of polyene action upon biological membranes.