Mise M, Arii S, Higashitsuji H, Furutani M, Monden K, Adachi Y, Funaki N, Fujita S, Ishiguro S
First Department of Surgery, Faculty of Medicine, Kyoto University, Japan.
Immunopharmacology. 1994 Jan-Feb;27(1):31-41. doi: 10.1016/0162-3109(94)90005-1.
The aim of this study was to investigate the augmentative effect of a streptococcal preparation, OK432, on the immunological competence of hepatic macrophages. We found that OK432 was distributed predominantly to hepatic macrophages after intravenous injection, and Northern blot analysis revealed that OK432 induced the gene expression of IL-1 alpha, beta, and TNF alpha in the liver. The induction of mRNAs was evident 1 h after the intravenous injection of OK432 and their accumulation reached a maximal level at 3 h. TNF production of hepatic macrophages was also increased by the intravenous injection of OK432. Furthermore, OK432 significantly increased the proportion of IL-2 receptor-positive hepatic macrophages. As for antitumor activity in the liver being augmented by OK432, the cytotoxic and cytostatic activity of hepatic macrophages from OK432-treated rats against tumor cells was significantly increased and OK432 markedly reduced the number of tumor nodules in the liver after the inoculation of tumor cells via the portal vein. These findings, which indicate that OK432 has various immuno-stimulating actions on hepatic macrophages, leading to the augmentation of antitumor activity in the liver, suggest that OK432 may be of some benefit in helping to prevent hepatic metastasis, at least in part, via its activation of hepatic macrophages.
本研究旨在探讨链球菌制剂OK432对肝巨噬细胞免疫能力的增强作用。我们发现，静脉注射后OK432主要分布于肝巨噬细胞，Northern印迹分析显示OK432可诱导肝脏中IL-1α、β及TNFα的基因表达。静脉注射OK432 1小时后mRNA诱导明显，3小时时其积累达到最高水平。静脉注射OK432也可增加肝巨噬细胞的TNF产生。此外，OK432可显著增加IL-2受体阳性肝巨噬细胞的比例。至于OK432增强肝脏的抗肿瘤活性，经OK432处理的大鼠肝巨噬细胞对肿瘤细胞的细胞毒性和细胞生长抑制活性显著增加，且OK432经门静脉接种肿瘤细胞后可显著减少肝脏中的肿瘤结节数量。这些结果表明OK432对肝巨噬细胞具有多种免疫刺激作用，从而导致肝脏抗肿瘤活性增强，提示OK432至少部分通过激活肝巨噬细胞可能有助于预防肝转移。
