Liver injury due to sequential activation of natural killer cells and natural killer T cells by carrageenan

Abstract

Background/Aims : Carrageenan is a high molecular weight polysaccharide and is widely used as a food additive for the solidification of plant oils and the thickening of many beverages. It is known that acute toxicity of carrageenan is possibly induced by the activation of phagocytic cells. We investigated other effects of carrageenan on lymphocytes in this study. Methods : Carrageenan was intraperitoneally injected once into mice and phenotypic and functional characterizations were conducted in various immune organs. Results : Natural killer (NK) cells were prominently activated in the liver, lungs, and spleen. A time-kinetic study showed sequential activation of NK and natural killer T (NKT) cells in the liver on days 3–10 after the injection. In parallel with the activation of NK and NKT cells in number, NK and NKT cytotoxicities were augmented. At this time, liver injury was induced, accompanied by massive hepatic necrosis and the elevation of transaminases. The in vivo elimination of NK cells reduced the liver injury induced by carrageenan. Direct binding of carrageenan onto NK cells was also demonstrated. Such a binding then induced a subsequent production of IFNγ. Perforin molecules of NK cells were responsible for this liver injury. Conclusions : These results suggest that not only phagocytic cells but also primitive lymphocyte (mainly NK cells) subsets might be important targets for the acute toxicity of carrageenan.