Chaudhuri G, Mukhopadhyay A, Basu S K
Institute of Microbial Technology, Chandigarh, India.
Biochem Pharmacol. 1989 Sep 15;38(18):2995-3002. doi: 10.1016/0006-2952(89)90007-5.
Methotrexate (Mtx) conjugated with maleylated bovine serum albumin (Mtx-MBSA) was taken up and degraded by cultured hamster peritoneal macrophages through the polyanion binding site for acetylated low density lipoprotein. Mtx-MBSA also eliminated intracellular amastigotes of Leishmania donovani in cultured hamster peritoneal macrophages about three times more efficiently than free Mtx. The antileishmanial effect of Mtx-MBSA on parasitized macrophages was blocked by MBSA, lysosomal inhibitors (chloroquine and monensin), and metabolic antagonists of Mtx (folic and folinic acids). The primary sites of accumulation of radioactivity of injected 125I-labeled Mtx-MBSA were the macrophage rich tissues, viz. liver and spleen. These results suggest that Mtx-MBSA would ensure rapid and effective killing of intracellular parasites harbored by macrophages. Furthermore, these results also indicate the feasibility of a general approach for rapid intracellular delivery of desired agents to macrophages for various purposes.
与马来酰化牛血清白蛋白结合的甲氨蝶呤（Mtx-MBSA）通过乙酰化低密度脂蛋白的聚阴离子结合位点被培养的仓鼠腹膜巨噬细胞摄取并降解。Mtx-MBSA在培养的仓鼠腹膜巨噬细胞中清除杜氏利什曼原虫的细胞内无鞭毛体的效率比游离Mtx高约三倍。Mtx-MBSA对受寄生虫感染的巨噬细胞的抗利什曼原虫作用被MBSA、溶酶体抑制剂（氯喹和莫能菌素）以及Mtx的代谢拮抗剂（叶酸和亚叶酸）阻断。注射的125I标记的Mtx-MBSA放射性积累的主要部位是富含巨噬细胞的组织，即肝脏和脾脏。这些结果表明，Mtx-MBSA将确保快速有效地杀死巨噬细胞内寄生的寄生虫。此外，这些结果还表明了一种通用方法的可行性，即可以将所需药物快速细胞内递送至巨噬细胞以用于各种目的。
