Activated macrophages are responsible for the tumor-inhibitory effect in mice receiving intravenous injection of OK-432.
Mouse spleen cells, either pretreated in vitro with 100 U/ml of OK-432-induced IFN gamma for 18 h or obtained from mice 24 or 48 h after i.v. injection of OK-432(100 micrograms/mouse), were examined for their anti-tumor effect by Winn's neutralization assay against Meth-A tumor cells in BALB/c mice. Spleen cells treated in vitro or obtained in vivo 24 h after i.v. injection clearly neutralized the growth of admixed Meth-A cells. Two booster injections of 200 U of IFN gamma near the tumor site accelerated this neutralizating effect. In order to determine the effector subpopulation, inhibitory spleen cells were treated with either anti-Thy-1 monoclonal antibody plus complement, anti-asialo GM1 serum plus complement or with adherence on plastic plates followed by Sephadex G-10 column treatment. The effector cell activity in Winn assay was lost only after the removal of macrophages through plastic plate adherence and Sephadex G-10 column treatment, but not after anti-Thy-1 or anti-asialo GM1 treatment, with either in vitro- or in vivo-treated spleen-cell populations. The growth of Meth-A cells was inhibited not only by these activated macrophages in Winn's assay, but also by adoptive transfer of OK-432-induced cytotoxic macrophages intralesionally 4 days after the implantation of 1 X 10(6) Meth-A cells. Our evidence suggests that the systemic action of OK-432 can be explained by the effect of induced IFNgamma, through the activation of macrophages.
D000818:Animals; D001688:Biological Products / Q000008:administration & dosage*; D002460:Cell Line; D002478:Cells, Cultured; D005260:Female; D007275:Injections, Intravenous; D007369:Interferon Inducers; D007371:Interferon-gamma / Q000276:immunology / Q000302:isolation & purification*; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology* / Q000637:transplantation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000473:pathology*; D010844:Picibanil / Q000008:administration & dosage*; D013154:Spleen / Q000166:cytology / Q000276:immunology*
D001688:Biological Products; D007369:Interferon Inducers; D010844:Picibanil; D007371:Interferon-gamma