EFFECT OF SPLENECTOMY ON HEPATIC METASTASIS OF COLON-CARCINOMA AND NATURAL-KILLER ACTIVITY IN THE LIVER

We have previously demonstrated that administration of killed streptoc occal preparation (OK432), a biological response modifier, increased t he number of asialo GM(1)-positive cells in the liver, enhanced NK act ivity of hepatic mononuclear cells, and reduced the number of hepatic metastases of colon 38 adenocarcinoma that were inoculated into the su perior mesenteric vein of C57BL/6 strain mice. In the present study, t o clarify the role of the spleen in immune surveillance of the liver, the effect of splenectomy on hepatic metastasis of colon carcinoma and on hepatic NK activity has been examined. The number of hepatic metas tasis increased in the splenectomized mice, compared with that in sham -operated mice, Administration of OK432 increased the number of asialo GM(1)-positive cells in the liver and enhanced NK activity of hepatic mononuclear cells in both groups, but NK activity of hepatic mononucl ear cells in the splenectomized mice was less than that of the sham-op erated mice, An enhanced NK activity of these cells was abolished by t reatment with anti-asialo-GM(1) antibody plus complement in vitro. Int erleukin-2 mRNA expression was increased in the spleen 2 hr after OK43 2 administration and persisted until 8 hr, but was scarcely noted in t he liver. On the other hand, NK activity of hepatic mononuclear cells in the asialo GM(1)-positive cell-depleted (previous administration of antiserum against asialo GM(1)) mice was enhanced after OK432 adminis tration in the sham operated and splenectomized mice, but an enhanced NK activity in these mice was only partially or not at all abolished b y treatment with anti-asialo GM(1) antibody plus complement in vitro, respectively. These results suggest that the spleen could play an impo rtant role in an immune surveillance of the liver, Ln addition, OK432 first enhanced NK activity of hepatic mononuclear cells, which are sen sitive to the antibody against asialo GM(1). However, when asialo GM(1 )-positive cells were depleted, OK432 enhanced NK activity of hepatic mononuclear cells, which are resistant to anti-asialo GM(1) serum.