脂质体两性霉素B对小鼠巨噬细胞和淋巴细胞的影响。
Effect of liposomal amphotericin B on murine macrophages and lymphocytes.
作者信息
Mehta R T, Mehta K, Lopez-Berestein G, Juliano R L
出版信息
Infect Immun. 1985 Feb;47(2):429-33. doi: 10.1128/iai.47.2.429-433.1985.
The effect of liposome-encapsulated amphotericin B on mouse macrophages and on T- and B-lymphocyte functions in vitro was compared with that of free amphotericin B. Liposomal amphotericin B was generally less toxic than the free form of the drug. Low concentrations of free amphotericin B completely inhibited the serum-dependent induction of transglutaminase, a marker for macrophage differentiation, and production of superoxide anion by macrophages, whereas encapsulation of the drug within liposomes protected the cells from these adverse effects. Liposomal amphotericin B did not affect the blastogenic response of T cells compared with the free drug, which was inhibitory at high concentrations. Antibody production in vivo was inhibited partially by both free and liposomal amphotericin B. These results thus suggest that encapsulation of amphotericin B in liposomes reduces the immunosuppressive effects exerted by free amphotericin B. This provides further justification for therapeutic use of liposomal amphotericin B in systemic fungal infections (G. Lopez-Berestein, R. Mehta, R. L. Hopfer, K. Mills, L. Kasi, K. Mehta, V. Fainstein, M. Luna, E. M. Hersh, and R. L. Juliano, J. Infect. Dis. 147:939-945, 1983).
将脂质体包裹的两性霉素B与游离两性霉素B在体外对小鼠巨噬细胞以及T淋巴细胞和B淋巴细胞功能的影响进行了比较。脂质体两性霉素B的毒性通常低于游离形式的药物。低浓度的游离两性霉素B完全抑制了转谷氨酰胺酶（巨噬细胞分化的标志物）的血清依赖性诱导以及巨噬细胞超氧阴离子的产生，而将药物包裹在脂质体内可保护细胞免受这些不利影响。与游离药物相比，脂质体两性霉素B不影响T细胞的增殖反应，游离药物在高浓度时具有抑制作用。游离和脂质体两性霉素B在体内均部分抑制抗体产生。因此，这些结果表明，将两性霉素B包裹在脂质体中可降低游离两性霉素B所产生的免疫抑制作用。这为脂质体两性霉素B在系统性真菌感染中的治疗应用提供了进一步的依据（G. 洛佩斯 - 贝雷斯坦、R. 梅塔、R. L. 霍普费尔、K. 米尔斯、L. 卡西、K. 梅塔、V. 法因斯坦、M. 卢娜、E. M. 赫什和R. L. 朱利亚诺，《传染病杂志》147:939 - 945, 1983）。
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