抗Mac-1单克隆抗体和细胞因子对利什曼原虫入侵和细胞内生存的抑制作用

目的：探索细胞内利什曼原虫的入侵、生存机制，为研制阻断利什曼原虫与巨噬细胞结合的新型抗利什曼药物以及利什曼病免疫预防和免疫治疗的研究提供理论基础。方法：采用抗Ｍａｃ １单克隆抗体（Ｍ１／７０和Ｍ１８／２）和重组的ＩＦＮ γ，ＴＮＦ α和ＩＬ ３处理巨噬细胞，观察经上述因子处理后的巨噬细胞对杜氏利什曼原虫前鞭毛体入侵和无鞭毛体在细胞内生存的影响。结果：经Ｍ１／７０和Ｍ１８／２单抗处理后巨噬细胞对杜氏利什曼原虫的易感性明显降低，其原虫感染率和受染巨噬细胞内入侵的原虫数量减低，原虫对巨噬细胞的入侵过程和速度也减慢。Ｍ１／７０和Ｍ１８／２两种单抗同时应用，则对原虫入侵巨噬细胞的抑制作用更为显著。通过对实验中所用的三种细胞因子活化巨噬细胞能力的观察发现，重组的ＩＦＮ γ或ＴＮＦ α均可激活巨噬细胞，提高巨噬细胞的杀原虫活性，且上述两种细胞因子联合对巨噬细胞的活化具有协同增强作用。但重组的ＩＬ ３不仅不能激活巨噬细胞而且尚抑制ＩＦＮ γ对巨噬细胞的活化作用。通过测定活化巨噬细胞内氧化氮产物（ＮＯ２）的生成量，观察ＮＯ２生成与巨噬细胞对原虫杀伤活性的关系，进一步探索了活化巨噬细胞对细胞内原虫的杀伤机制。结论：作用于巨噬细?

Inhibition effect of anti Mac 1 monoclonal antibodies and cytokines on the invasion of host macrophages by Leishmania parasit

Objective:To study the effect of anti Mac 1 monoclonal antibodies and cytokines on the invasion of host macrophages by Leishmania parasite.Methods:The phagocytosis of Leishmania donovani by activated macrophages was observed after the cultured macrophages were in vitro treated with anti Mac 1 McAbs(M 1/70 and M 18/2 ) and recombinant IFN γ,TNF α,IL 3.Results:The percentage of the infected macrophages and the number of the invading parasites were significantly decreased after the macrophages were treated with the above McAbs.The phagocytic process of macrophages toward parasites was found decelerated too.When macrophages were treated with both M 1/70 and M 18/2 ,phagocytosis of parasites by the macrophages was more distinctly inhibited than those treated by either of the two McAbs.The effect of activated macrophages on Leishmania donovani amastigotes and nitrite(NO 2) release were determined by in vitro inducement of macrophage activation with recombinant IFN γ ,TNF α , IL 3. The results showed that IFN γ or TNF α at 40 000 U/L was able to induce a significant but modest level of macrophage activity,and synergistic effect of IFN γ and TNF α was apparent in the induction of macrophage activation.However,IL 3 was not able to activate macrophages but to inhibit the effect of IFN γ on macrophager.Conclusion:These data indicated that the anti macrophage surface molecules,Mac 1 McAbs (M 1/70 and M 18/2 and recombinant IFN γ and TNF α might inhibit the phagocytosis of macrophages to Leishmania parasite.