Influence of Desialylation on the Interaction of Red Blood Cells with a Hemotoxic Partly Quaternized Tertiary Polyamine

Abstract

Partly quaternized poly[thio-1-(N,N-diethyl-aminomethyl) ethylene] polycations (Q-P(TDAE)_x) interact electrostatically with the membrane of human red blood cells (RBC) and are highly toxic when given intravenously (i.v.). In order to study the influence of sialic acid negative charges on the hemagglutination and hemolysis induced by Q-P(TDAE)₁₁, RBC were desialylated using neuraminidase. Desialylation had little influence on Q-P(TDAE)₁₁-induced agglutination. It was concluded that this feature resulted from two opposite phenomena consecutive to the decrease of the negative charge of the cell membrane. The first was a decrease of electrostatic attraction between Q-P(TDAE)₁₁ and RBC resulting in less aggregation. The second was reduction of electrostatic repulsions between RBC, which made RBC clustering relatively easier, thus counteracting the first effect. On the other hand, the hemolyzing effect of Q-P(TDAE)₁₁ on desialyated RBC was lower than that observed for native RBC in the presence of serum and plasma, whereas it was greater in a protein-free model medium. This study confirmed that electrostatic interactions between polyanionic RBC and polycations are one of the crucial determinants, but not the only one, for polycation-induced perturbations of RBC. Among these effects, massive hemagglutination is likely to be responsible for the embolism and the ensuing animal death previously observed soon after the i.v. administration of Q-P(TDAE)₁₂ solutions.