Interaction of Plasma Proteins and Lipoproteins with Amphotericin B

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Abstract
Amphotericin B (AmB) bound to the cholesterol in lipoproteins, as determined by co-migration in density gradient ultracentrifugation and changes in the circular dichroic spectrum. The saturation curve and Scatchard plots obtained with circular dichroism suggested that 4-10 cholesterol molecules in low-density lipoproteins bound to 1 molecule of AmB. AmB interacted more rapidly with low- and very-low-density lipoproteins than with high-density lipoproteins; the circular dichroic spectrum of the complexed species was the same in all 3 cases. AmB also bound to other proteins in blood; much higher concentrations of these proteins than of lipoproteins were needed for comparable binding. Interaction with lipoproteins stabilized the antifungal activity of AmB. Interaction with lipoproteins and with much higher concentrations of other proteins in blood also inhibited the effects of AmB on red blood cells, which contain cholesterol in their plasma membranes, but not the effects on Candida albicans, whose membranes contain ergosterol. An appropriate inference is that, when used clinically, AmB circulates in blood bound to lipoproteins and other proteins. The toxic and therapeutic effects of AmB in clinical situations are thus contingent on competitive interactions between sterol-containing cellular membranes of the host and the parasite and components of blood, such as lipoproteins and proteins.

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