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脂质体相关蛋白抗原介导的免疫反应。IV. 囊泡包裹的甲氨蝶呤对抗体形成的调节。

Immune response mediated by liposome-associated protein antigens. IV. Modulation of antibody formation by vesicle-encapsulated methotrexate.

作者信息

Shek P N, Lopez N G, Heath T D

出版信息

Immunology. 1986 Jan;57(1):153-7.

PMID:3510967
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1453890/
Abstract

Large unilamellar reverse-phase evaporation vesicles (REV) were used as a heterobifunctional carrier for a pharmacologically active agent and a protein antigen. Methotrexate (MTX) was encapsulated in the hydrophilic compartment of liposomal REV with or without surface-conjugated bovine serum albumin (BSA) antigen. The administration of MTX encapsulated within BSA-coated vesicles (MTX.REV-BSA) could either enhance or depress the anti-BSA plaque-forming cell (PFC) response in mice. On the other hand, the administration of MTX entrapped in plain vesicles (MTX.REV) produced essentially a suppressive effect on the PFC response stimulated by the simultaneous injection of a separate antigen, e.g. vesicle-conjugated BSA (REV-BSA). This suppression of the antibody response occurred, whether MTX.REV was injected 1 day before, during, or 1 day after the immunization with an antigen. These results indicate that liposome-encapsulation of a very limited drug dose can modify the immunobiological effect of the drug which, when presented in its free form at the same dose, exerts no appreciable action on the engendered immune response. Thus, the modulation of the immune response by a liposome-encapsulated drug appears to be influenced by the drug dose can modify the immunobiological effect of the drug which, when presented in its free form.

摘要

大单层反相蒸发囊泡(REV)被用作药理活性剂和蛋白质抗原的异双功能载体。甲氨蝶呤(MTX)被包裹在脂质体REV的亲水隔室中,脂质体表面有或没有偶联牛血清白蛋白(BSA)抗原。给予包裹在BSA包被囊泡中的MTX(MTX.REV-BSA)可增强或抑制小鼠抗BSA空斑形成细胞(PFC)反应。另一方面,给予包裹在普通囊泡中的MTX(MTX.REV)对同时注射单独抗原(如囊泡偶联的BSA,REV-BSA)刺激的PFC反应产生基本的抑制作用。无论MTX.REV是在抗原免疫前1天、免疫期间还是免疫后1天注射,抗体反应的这种抑制都会发生。这些结果表明,极少量药物剂量的脂质体包裹可以改变药物的免疫生物学效应,而相同剂量的游离形式药物对产生的免疫反应没有明显作用。因此,脂质体包裹药物对免疫反应的调节似乎受药物剂量的影响,药物剂量可以改变药物的免疫生物学效应,而药物以游离形式存在时则不然。

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本文引用的文献

1
Protein measurement with the Folin phenol reagent.使用福林酚试剂进行蛋白质测定。
J Biol Chem. 1951 Nov;193(1):265-75.
2
Immune response mediated by liposome-associated protein antigens. I. Potentiation of the plaque-forming cell response.脂质体相关蛋白抗原介导的免疫反应。I. 对空斑形成细胞反应的增强作用。
Immunology. 1982 Feb;45(2):349-56.
3
The role of macrophages in promoting the antibody response mediated by liposome-associated protein antigens.巨噬细胞在促进脂质体相关蛋白抗原介导的抗体反应中的作用。
Immunol Lett. 1982;5(6):305-9. doi: 10.1016/0165-2478(82)90118-3.
4
Immune response mediated by liposome-associated protein antigens. II. Comparison of the effectiveness of vesicle-entrapped and surface-associated antigen in immunopotentiation.脂质体相关蛋白抗原介导的免疫反应。II. 囊泡包裹抗原与表面结合抗原在免疫增强效果上的比较。
Immunology. 1982 Dec;47(4):627-32.
5
Specific enhancement of drug delivery to AKR lymphoma by antibody-targeted small unilamellar vesicles.通过抗体靶向小单层囊泡特异性增强药物向AKR淋巴瘤的递送。
Cancer Res. 1984 May;44(5):1880-6.
6
Antibody-targeted liposomes: increase in specific toxicity of methotrexate-gamma-aspartate.抗体靶向脂质体:甲氨蝶呤-γ-天冬氨酸特异性毒性的增强
Proc Natl Acad Sci U S A. 1983 Mar;80(5):1377-81. doi: 10.1073/pnas.80.5.1377.
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Immunologic response to protein immobilized on the surface of liposomes via covalent azo-bonding.
Biochim Biophys Acta. 1984 May 30;772(3):288-94. doi: 10.1016/0005-2736(84)90145-7.
8
Immune response mediated by liposome-associated protein antigens. III. Immunogenicity of bovine serum albumin covalently coupled to vesicle surface.脂质体相关蛋白抗原介导的免疫反应。III. 共价偶联至囊泡表面的牛血清白蛋白的免疫原性。
Immunology. 1983 Sep;50(1):101-6.
9
Targeting of drugs: implications in medicine.药物靶向:对医学的影响。
Lancet. 1981 Aug 1;2(8240):241-6. doi: 10.1016/s0140-6736(81)90486-4.
10
Selective alteration of immunocompetence with methotrexate and 5-fluorouracil.甲氨蝶呤和5-氟尿嘧啶对免疫能力的选择性改变。
Cancer Res. 1974 Jan;34(1):124-8.