Immunosuppressive effects of the macrolide antibiotic bafilomycin towards lymphocytes and lymphoid cell lines.

The effects of bafilomycin macrolide antibiotics on primary lymphocytes and on tumor cell lines were investigated. Bafilomycin A markedly suppressed DNA, RNA, and protein synthesis in splenocyte cultures of several inbred mouse strains. Bafilomycins were also inhibitory towards cultures of concanavalin A- or lipopolysaccharide-activated murine spleen cells, and inhibited the mitogen-induced differentiation of B lymphocytes into immunoglobulin-secreting plasma cells. Corresponding results were obtained in human cell cultures. A hydrolysis product of the bafilomycin molecule was inactive. Bafilomycin also inhibited the growth of various lymphoid cell lines, the B cell line BCL1, the macrophage cell lines J774 and P338D1, and the T cell line EL4. The sensitivity of the tumor cell lines increased when, simultaneously with bafilomycin, mitogens were applied to the cell cultures. The immunosuppressive action of cyclosporin A could be enhanced by bafilomycin, which could be of importance for the elucidation of the molecular mechanism of T cell suppression, and for applied medical research.