CYTOLYSIS OF HUMAN ERYTHROCYTES BY A COVALENT ANTIBODY-SELENIUM IMMUNOCONJUGATE

A selenium (Se)-containing immunoconjugate of a human anti-erythrocyte membrane antibody (Ab-Se) has been synthesized via oxidation of the c arbohydrate moieties of the antibody and covalent coupling with seleno cystamine. The isolated Ab-Se immunoconjugate is shown to be more hemo lytic than is selenocystamine when expressed on equivalent selenium ba sis. Native antibody preincubated with the human erythrocytes prevente d hemolysis induced by the Ab-Se immunoconjugate. As observed microsco pically, the Ab-Se immunoconjugate caused extensive damage to the eryt hrocyte membrane and lysis. The cytotoxicity of Se toward the human er ythrocytes is believed to be caused initially by the localized generat ion of superoxide (O-2(.-)) within the cell membrane. This is the firs t demonstration of site-directed immunoselectivity of Se cytotoxicity and demonstrates the potential for a free radical pharmacology based o n localized Se-generated O-2(.-).