Cytotoxicity of immune guinea-pig cells. II. The mechanism of macrophage cytotoxicity

Abstract

Macrophages from immune guinea-pigs, as well as macrophages from non-immune animals in the presence of specific antibody, were cytotoxic to chicken erythrocytes. Elution from macrophages produced a γ₂-globulin which enabled non-immune macrophages to form rosettes with chicken erythrocytes, to phagocytose, and to show cytotoxicity towards such cells. This antibody was target-cell specific; it also rendered spleen cells cytotoxic. Isoelectric focusing of antiserum gave a peak of cytophilic antibody at pH 6.8–7.6 which proved to be in the γ₂ region.

The significance of phagocytosis for the cytotoxic process was examined with the aid of cytochalasin B which inhibited macrophage—phagocytosis, but produced enhanced cytotoxicity in this sytem. At the same time there was greatly increased release of lysosomal enzymes from macrophages in the presence of target cells. It is considered that, although phagocytosis is of significance for macrophage cytotoxicity, target cell destruction can also occur by the liberation of lysosomal enzymes from the plasma membrane into the target cell when this is in close surface contact.