一种新的合成酰基三肽及其类似物包裹在脂质体中激活大鼠肺泡巨噬细胞至肿瘤细胞毒性状态。

Activation by a new synthetic acyltripeptide and its analogs entrapped in liposomes of rat alveolar macrophages to the tumor cytotoxic state.

作者信息

Sone S, Mutsuura S, Ogawara M, Utsugi T, Tsubura E

出版信息

Cancer Immunol Immunother. 1984;18(3):169-73. doi: 10.1007/BF00205507.

DOI:10.1007/BF00205507

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11039237/

Abstract

FK-565 (heptanoyl-gamma-D-Glu-(L-meso-a, epsilon-A2pm (L)-D-AlaOH) is a synthetic acyltripeptide closely resembling cell wall peptidoglycan peptides of Streptomyces in structure. Alveolar macrophages (AM) lavaged from lungs of F344 rats were activated by in vitro treatment with FK-565 and its derivatives at concentrations of 1-50 micrograms/ml medium, and the activated AM killed syngeneic mammary adenocarcinoma cells. When FK-565 and related compounds were encapsulated in multilamellar (MLV) liposomes composed of phosphatidylcholine and phosphatidylserine, dose-response experiments showed that they were about 800 times more effective than the free compounds in activating AM. Liposome-encapsulated FK-565 and its analogs caused significant activation of AM within 4 h. These data indicated that acyltripeptide and its analogs encapsulated in liposomes are more efficient than the free compounds in rendering AM tumoricidal.

摘要

FK-565（庚酰基-γ-D-谷氨酸-（L-内消旋-α，ε-二氨基庚二酸（L）-D-丙氨酸）是一种合成酰基三肽，其结构与链霉菌的细胞壁肽聚糖肽非常相似。从F344大鼠肺中冲洗出的肺泡巨噬细胞（AM），在体外以1-50微克/毫升培养基的浓度用FK-565及其衍生物处理后被激活，并且激活后的AM杀死了同基因的乳腺腺癌细胞。当FK-565和相关化合物被包裹在由磷脂酰胆碱和磷脂酰丝氨酸组成的多层脂质体（MLV）中时，剂量反应实验表明，它们在激活AM方面比游离化合物有效约800倍。脂质体包裹的FK-565及其类似物在4小时内引起了AM的显著激活。这些数据表明，包裹在脂质体中的酰基三肽及其类似物在使AM具有杀肿瘤能力方面比游离化合物更有效。

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本文引用的文献

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J Immunol. 1980 Dec;125(6):2454-60.

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Therapy of spontaneous metastases by intravenous injection of liposomes containing lymphokines.通过静脉注射含有淋巴因子的脂质体治疗自发性转移瘤。

Science. 1980 Jun 27;208(4451):1469-71. doi: 10.1126/science.7384789.

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Tumor cytotoxicity of rat alveolar macrophages activated in vitro by endotoxin.内毒素体外激活的大鼠肺泡巨噬细胞的肿瘤细胞毒性

J Reticuloendothel Soc. 1980 Mar;27(3):269-79.

4

Rat alveolar macrophages are susceptible to activation by free and liposome-encapsulated lymphokines.大鼠肺泡巨噬细胞易被游离的和脂质体包裹的淋巴因子激活。

J Immunol. 1980 May;124(5):2197-202.

5

Activation of rat alveolar macrophages to the tumoricidal state in the presence of progressively growing pulmonary metastases.在肺部转移瘤逐渐生长的情况下，将大鼠肺泡巨噬细胞激活至杀瘤状态。

Cancer Res. 1981 Jun;41(6):2401-6.

6

Studies on a new immunoactive peptide, FK-156. IV. Synthesis of FK-156 and its geometric isomer.新型免疫活性肽FK-156的研究。IV. FK-156及其几何异构体的合成。

J Antibiot (Tokyo). 1982 Oct;35(10):1300-11. doi: 10.7164/antibiotics.35.1300.

7

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J Antibiot (Tokyo). 1982 Oct;35(10):1280-5. doi: 10.7164/antibiotics.35.1280.

8

Inhibition of lung metastases in mice bearing a malignant fibrosarcoma by treatment with liposomes containing human C-reactive protein.用人C反应蛋白脂质体治疗对患有恶性纤维肉瘤的小鼠肺转移的抑制作用。

Cancer Res. 1982 Dec;42(12):5084-8.

9

Human alveolar macrophages: potentiation of their tumoricidal activity by liposome-encapsulated muramyl dipeptide.人肺泡巨噬细胞：脂质体包裹的胞壁酰二肽增强其杀肿瘤活性。

J Immunol. 1982 Sep;129(3):1313-7.

10

The role of plasma membrane receptors and the kinetics of macrophage activation by lymphokines encapsulated in liposomes.质膜受体的作用以及脂质体包裹的淋巴因子激活巨噬细胞的动力学。

Cancer Res. 1981 Feb;41(2):495-504.

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