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.
Heinle
S
S
Institut für Immunbiologie, Universität Freiburg, Fed. Rep. of Germany.
Stünkel
K
K
Zähner
H
H
Drautz
H
H
Bessler
W G
WG
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D055598:Chemical Phenomena; D002621:Chemistry; D003524:Cyclosporins / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007166:Immunosuppressive Agents; D007783:Lactones / Q000494:pharmacology; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology; D008223:Lymphoma; D018942:Macrolides; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008934:Mitogens / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects; D014407:Tumor Cells, Cultured
D000900:Anti-Bacterial Agents; D003524:Cyclosporins; D007166:Immunosuppressive Agents; D007783:Lactones; D018942:Macrolides; D008934:Mitogens; C057620:bafilomycin A