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Our previous work showed that SEP,a novel glucan isolated from the eggs of sea urchins,Strongylocentrotus nudus,had remarkable anti-tumor activity. To elucidate the mechanism of the antitumor activity,the immunomodulatory activity of SEP was investigated. The in vivo experiment results showed that SEP remarkably enhanced spleen and thymus index in S180-bearing mice,and also stimulated ConA-induced splenocyte proliferation. Immunomodulatory activity assay in vitro indicated SEP could significantly enhance the mouse splenocyte proliferation in a dose-dependent manner. According to comitogenic activity tests,SEP showed significant comitogenic activities and adjuvant properties. We also demonstrated that SEP had a unique mode of immunostimulation with regard to its cell-type specificity,i.e.,SEP markedly stimulated B and T cell proliferation; however the influence on B cells was greatly weaker than that on T cells. IL-2,TNF-a,and IFN-? mRNA expression was upregulated after the mouse splenocytes were treated by SEP,indicating that Th1 cell was the primary cellular target affected by SEP on T lymphocyte. SEP enhanced production of nitric oxide(NO),upregulated mRNA expression of inducible nitric oxide synthase(iNOS)in peritoneal macrophages in a dose-dependent manner. In addition,SEP did not show direct toxicity to tumor cells. Consequently,the anti-tumor effect of SEP was related to stimulating host immunity/ enhancing the immune system functions.