Prodigiosin 25-C suppression of cytotoxic T cells in vitro and in vivo similar to that of concanamycin B, a specific inhibitor of vacuolar type H(+)-ATPase.
The effects of prodigiosin 25-C (PrG) which preferentially suppresses cytotoxic T cells (CTL), was examined in comparison with concanamycin B (CMB), a specific inhibitor of vacuolar type H(+)-ATPase (V-ATPase). PrG and CMB directly inhibited the cytotoxic function of CTL and neutralized acidic organelles of CTL in vitro. In addition, PrG or CMB was injected in C57BL/6 mice after immunization with an allogeneic mastocytoma, P815. PrG and CMB inhibited the killing activity of CTL against the tumor and reduced the population of CD8+ cells without affecting CD4+ and B220+ populations in the spleen. PrG and CMB had only a negligible effect on antibody production induced by sheep red blood cells (SRBC) and mitogenic responses of lymphocytes. These results suggest that PrG and CMB have similar immunosuppressive properties at least through their inhibitory effects on acidification of intracellular organelles required for the effective function of CTL.
Lee
M H
MH
Department of Bioengineering, Tokyo Institute of Technology, Yokohama, Japan.
Kataoka
T
T
Magae
J
J
Nagai
K
K
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D018942:Macrolides; D051379:Mice; D008810:Mice, Inbred C57BL; D011353:Prodigiosin / Q000031:analogs & derivatives* / Q000494:pharmacology; D013154:Spleen / Q000166:cytology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D025262:Vacuolar Proton-Translocating ATPases
D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D018942:Macrolides; C077331:prodigiosin 25C; C036979:concanamycin B; D000251:Adenosine Triphosphatases; D025262:Vacuolar Proton-Translocating ATPases; D011353:Prodigiosin