A Two-Step Mechanism for the Interaction of Re Lipopolysaccharide with Erythrocyte Membranes

In this report, a unique model system that allows the investigation of the interaction of lipopolysaccharide (LPS) with erythrocyte membranes is described. Rabbit red blood cells exposed to S. minnesota (Re mutant) R595 LPS were rendered sensitive to the cationic antibiotic polymyxin B in a manner independent of the temperature of incubation of erythrocytes with LPS (subsequent addition of polymyxin B induced hemolysis of erythrocytes sensitized with LPS). Following sensitization of red blood cells with R595 LPS, a time-dependent decrease in susceptibility of the cells to polymyxin B-mediated hemolysis occurred, which was shown not to be the result of dissociation of LPS from rabbit erythrocytes. The demonstration that the decrease in sensitivity of red blood cells to polymyxin B was dependent on the temperature of incubation of LPS with red blood cells is not inconsistent with the proposal that the decrease in sensitivity is attributable to a hydrophobic rearrangement of lipid-rich R595 LPS within the lipid bilayer of the erythrocyte membrane. The importance of this putative rearrangement of LPS within cell membrane in cellular triggering of LPS is unknown.