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Activated macrophages are responsible for the tumor-inhibitory effect in mice receiving intravenous injection of OK-432

✍ Scribed by Motoo Saito; Masaki Nanjo; Etsuko Aonuma; Tetsuo Noda; Ichiro Nakadate; Takusaburo Ebina; Nakao Ishida


Publisher
John Wiley and Sons
Year
1984
Tongue
French
Weight
601 KB
Volume
33
Category
Article
ISSN
0020-7136

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✦ Synopsis


Mouse spleen cells, either pretreated in vitrowith 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 fig/ 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 vitroor 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-I monoclonal antibody plus complement, antiasialo GM, serum plus complement or with adherence on plastic plates followed by Sephadex G-I0 column treatment. The effector cell activity in Winn assay was lost only after the removal of macrophages through plastic plate adherence and Sephadex G-I0 column treatment, but not after anti-Thy-I or anti-asialo GM, treatment, with either in vitro-or in vivcztreated spleen-cell populations. The growth of Meth-A cells was inhibited not only by these activated macrophages in Winn's assay, but also by adop tive transfer of OK-432-induced cytotoxic macrophages intralesionally 4 days after the implantation of I X lo6 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.