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Abstract Resealed human erythrocyte ghosts were used as model target cells to study membrane damage induced by effector cells in antibody-dependent cell-mediated cytotoxicity (ADCC). The release of the water soluble dye carboxyfluorescein (CF) from ghosts was shown to parallel the lysis of intact cell targets with regard to requirements for effector cells, antibody binding, and divalent ions. The release of soluble fluorescent markers resealed inside ghost targets was measured in a series of double label experiments with CF and rhodamine-labeled macromolecules. A sharp size dependence of marker release was observed: human lymphocyte effector cells caused the release of all protein and dextran markers below 500,000 daltons to the same extent as CF. Both protein and dextran markers above this size, however, were not released. With neutrophils as ADCC effectors, protein markers of the same size were released, whereas monocytes gave a slightly smaller m.w. cutoff. Lymphocyte effectors did not mediate CF release from smaller vesicle targets derived from whole ghosts. Treatment of whole ghost targets by antibody and complement also showed a sharp size cutoff for release of markers, but at about 10 × lower m.w. for both proteins and dextrans. The results strongly suggest that ADCC effector cells inflict lethal damage to target cells by causing the formation of aqueous pores in the target membrane, and that such pores are larger than those formed by complement.
Simone et al. (Fri,) studied this question.