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用含甲氨蝶呤的载抗体荧光脂质体评估T和B淋巴细胞表面分子的差异性内吞作用。

Differential endocytosis of T and B lymphocyte surface molecules evaluated with antibody-bearing fluorescent liposomes containing methotrexate.

作者信息

Machy P, Barbet J, Leserman L D

出版信息

Proc Natl Acad Sci U S A. 1982 Jul;79(13):4148-52. doi: 10.1073/pnas.79.13.4148.

Abstract

Antibody-bearing fluorescent liposomes containing methotrexate became bound to cells expressing determinants recognized by the antibody. The number of bound liposomes could be evaluated by fluorometry, and the internalization of liposomes was evaluated by the methotrexate-mediated inhibition of radio-labeled deoxyuridine incorporation. The effect of methotrexate transferred from the liposomes into the cells was a function not of the number of liposomes bound but of the nature of the cells and of the target molecules. Liposomes bearing antibodies with specificity for the H-2K or Mr 94,000 and 180,000 molecules were much more effective at drug delivery into T than B cells, even though these determinants were expressed by both cell types. B cells were more sensitive to the effect of methotrexate in anti-H-2 I-A and I-E liposomes than in anti-H-2K liposomes. Inhibition of the methotrexate effect by NH4Cl suggested that methotrexate entered the cell by endocytosis of the liposomes. The results are consistent with differential internalization of H-2K, I-A, I-E, and Mr 94,000 and 180,000 cell surface molecules by mitogen-stimulated T and B cells.

摘要

含有甲氨蝶呤的携带抗体的荧光脂质体与表达该抗体所识别的决定簇的细胞结合。结合的脂质体数量可通过荧光测定法评估,脂质体的内化作用则通过甲氨蝶呤介导的对放射性标记脱氧尿苷掺入的抑制作用来评估。从脂质体转移到细胞内的甲氨蝶呤的作用不是取决于结合的脂质体数量,而是取决于细胞的性质和靶分子的性质。携带对H-2K或分子量为94,000和180,000的分子具有特异性的抗体的脂质体,在将药物递送至T细胞而非B细胞方面更有效,尽管这两种细胞类型都表达这些决定簇。B细胞对抗H-2 I-A和I-E脂质体中甲氨蝶呤的作用比对抗H-2K脂质体更敏感。氯化铵对甲氨蝶呤作用的抑制表明,甲氨蝶呤是通过脂质体的内吞作用进入细胞的。这些结果与有丝分裂原刺激的T细胞和B细胞对H-2K、I-A、I-E以及分子量为94,000和180,000的细胞表面分子的差异内化作用一致。

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