Influence of desialylation on the interaction of red blood cells with a hemotoxic partly quaternized tertiary polyamine

Partly quaternized poly[thio-1-(N,N-diethyl-aminomethyl) ethylene] polycati ons (Q-P(TDAE)(x)) interact electrostatically with the membrane of human re d blood cells (RBC) and are highly toxic when given intravenously (i.v.). I n order to study the influence of sialic acid negative charges on the hemag glutination and hemolysis induced by Q-P(TDAE)(11), RBC were desialylated u sing neuraminidase. Desialylation had little influence on Q-P(TDAE)(11)-ind uced agglutination. It was concluded that this feature resulted from two op posite 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 reduct ion of electrostatic repulsions between RBC, which made RBC clustering rela tively 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 o bserved for native RBC in the presence of serum and plasma, whereas it was greater in a protein-free model medium. This study confirmed that electrost atic interactions between polyanionic RBC and polycations are one of the cr ucial determinants, but not the only one, for polycation-induced perturbati ons of RBC. Among these effects, massive hemagglutination is likely to be r esponsible for the embolism and the ensuing animal death previously observe d soon after the i.v. administration of Q-P(TDAE)(12) solutions.