Swainsonine, an inhibitor of glycoprotein processing, enhances cytotoxicity of large granular lymphocytes.

In the present study we investigated the effects of inhibitors of glycoprotein processing on cytotoxicity of human large granular lymphocytes (LGL). The incubation of LGL for 36 h with 0.5 microgram/ml swainsonine (SW), which is an inhibitor of mannosidase II, resulted in the augmentation of cytotoxicity of LGL against an NK-resistant colon carcinoma cell line (Colo-320DM) without increase of binding frequency of LGL to target cells or of cell proliferation. The enhanced cytotoxicity was associated with increased binding of concanavalin A to SW-treated LGL. The augmentation of cytotoxicity was also seen by 1-deoxymannojirimycin (1-DMN), an inhibitor of mannosidase I, but much higher amounts of this agent were needed to get the same level of augmentation as that with SW. Other inhibitors of glycoprotein processing such as castanospermine and 1-deoxynojirimycin (1-DN) did not show any augmentative effects on LGL cytotoxicity. The enhancement of cytotoxicity by SW was abolished by the addition of rabbit anti-human interleukin (IL-2) antibody to the culture. This result suggests that IL-2 is involved in the augmentation of cytotoxicity of LGL by SW. The presence of SW in the culture of LGL together with IL-2 also enhanced LAK generation compared to that with IL-2 alone. Thus, our results suggest that SW should be recognized as an efficient immunopotentiator and that modulation of carbohydrate moieties elicited by SW may shed further light on the mechanism of LGL activation.