Petrov A B, Kolenko V M, Koshkina N V, Zakirov M M, Bugaev L V, Semenova I B, Wiertz E J, Poolman J T
Mechnikov Research Institute for Vaccines and Sera, Moscow, Russia.
Vaccine. 1994 Sep;12(12):1064-70. doi: 10.1016/0264-410x(94)90174-0.
The immunomodulating action of Neisseria meningitidis lipopolysaccharide (LPS) incorporated into liposomes and the activation of different populations of immunocompetent cells or the secretion of cytokines were studied. LPS stimulated an anti-sheep red blood cell (SRBC) plaque-forming cell response in the spleen of mice after simultaneous injection of LPS and SRBC but if LPS was administered 3 days before the immunization with SRBC the response to SRBC was strongly suppressed. After the incorporation of LPS into liposomes the stimulation index was increased from 6 to 19 and the liposomal LPS did not suppress the immune response to SRBC. The incorporation of LPS into liposomes leads to enhancement of B-mitogenic properties of LPS, as liposomal LPS stimulated the proliferation of splenocytes in mice better than free LPS and has no influence on the thymocytes. The liposomal LPS induced more prolonged and significant accumulation of IgM-secreting cells in the spleen of mice in comparison with the free LPS. Liposomal LPS also induced more active accumulation of IFN-gamma in human peripheral blood mononuclear cells and less active accumulation of monokines, contributing to the realization of the toxic properties of endotoxin (IL-1 alpha, TNF-alpha, IL-6 and GM-CSF). These results demonstrated that the incorporation of N. meningitidis LPS into liposomes dramatically changed its immunomodulating activity. The data obtained are important for the construction of an adjuvant formulation for synthetic immunogens capable of inducing genetically unrestricted immune responses.
研究了包裹于脂质体中的脑膜炎奈瑟菌脂多糖（LPS）的免疫调节作用以及不同免疫活性细胞群的激活或细胞因子的分泌。在同时注射LPS和绵羊红细胞（SRBC）后，LPS刺激了小鼠脾脏中抗绵羊红细胞（SRBC）的空斑形成细胞反应，但如果在接种SRBC前3天给予LPS，则对SRBC的反应受到强烈抑制。将LPS包裹于脂质体后，刺激指数从6增加到19，且脂质体LPS不会抑制对SRBC的免疫反应。LPS包裹于脂质体后导致LPS的B细胞促有丝分裂特性增强，因为脂质体LPS比游离LPS更好地刺激了小鼠脾细胞的增殖，且对胸腺细胞无影响。与游离LPS相比，脂质体LPS在小鼠脾脏中诱导分泌IgM的细胞积累更持久且显著。脂质体LPS还诱导人外周血单个核细胞中IFN-γ更活跃地积累，而诱导促炎单核因子（有助于内毒素毒性特性实现的IL-1α、TNF-α、IL-6和GM-CSF）的积累活性较低。这些结果表明，将脑膜炎奈瑟菌LPS包裹于脂质体中显著改变了其免疫调节活性。所获得的数据对于构建能够诱导基因非限制性免疫反应的合成免疫原的佐剂制剂具有重要意义。
