ANTISERUM TO LEUCOCYTE LYSOSOMES : ITS CYTOTOXIC, GRANULOLYTIC, AND HEMOLYTIC ACTIVITIES

Antisera to rabbit polymorph granules and to rabbit erythrocytes have been prepared in guinea pigs. Both antigranule and antierythrocyte sera are hemolytic and both exhibit striking cytotoxicity on leucocytes. The sequence of toxic events, as observed by phase contrast cinemicrophotography and electron microscopy, consists of explosive granule lysis, cell swelling, cytoplasmic liquifaction, and nuclear fusion. Other rabbit cells are also susceptible to these cytotoxic effects, but cells, including polymorphs, of other mammals are not. Cytotoxic action of the antisera requires, in addition to the antibody, heat-labile serum factors and divalent cations, suggesting that the action is a combined one of antibody and complement. The morphologic observations have been supported by biochemical studies demonstrating release into the medium of granule-bound hydrolases following exposure of polymorphs or of isolated granules to the antigranule or antierythrocyte sera. Granulolytic activity of the antisera can be reduced or removed by absorption with either rabbit leucocyte granules or with erythrocytes, indicating that leucocyte granules and erythrocytes have an identical or similar membrane constituent. The observations lend support to the notion that lysosomal hydrolases may exert autolytic effects in some situations.