Aramaki Y, Takano S, Arima H, Tsuchiya S
School of Pharmacy, Tokyo University of Pharmacy and Life Science, Hachioji, Japan.
Pharm Res. 2000 May;17(5):515-20. doi: 10.1023/a:1007552529280.
Liposomes are of considerable interest as drug carriers and immunoadjuvants. However, few investigators have studied the changes exerted by liposomes in the cells with which they interact. The purpose of this study was to investigate whether liposomes induce apoptosis in B cells.
The mouse immature B cell line WEHI 231 cells and mouse splenic B cells were treated with liposomes, and the induction of apoptosis was evaluated by monitoring changes in DNA content, DNA fragmentation and chromatin condensation by flow cytometry, agarose gel electrophoresis and by morphological investigation.
Cationic liposomes induced apoptosis in WEHI 231 cells, but neutral and anionic liposomes did not. A contact time of 30 min between WEHI 231 cells and cationic liposomes was sufficient to induce apoptosis, and 80% of the cells showed hypodiploid DNA content. Apoptosis induced by cationic liposomes composed of stearylamine was inhibited by addition of the oxidant scavenger, N-acetyl-cysteine.
Cationic liposomes induced apoptosis in WEHI 231 cells, and the production of reactive oxygen species is important in the regulation of apoptosis induced by cationic liposomes. It is well known that cationic liposomes show cytotoxicity, and apoptosis may be one of the causes of this toxicity.
脂质体作为药物载体和免疫佐剂备受关注。然而,很少有研究者研究脂质体与它们相互作用的细胞所产生的变化。本研究的目的是调查脂质体是否诱导B细胞凋亡。
用脂质体处理小鼠未成熟B细胞系WEHI 231细胞和小鼠脾脏B细胞,并通过流式细胞术、琼脂糖凝胶电泳监测DNA含量、DNA片段化和染色质凝聚的变化以及通过形态学研究来评估凋亡的诱导情况。
阳离子脂质体诱导WEHI 231细胞凋亡,但中性和阴离子脂质体则不会。WEHI 231细胞与阳离子脂质体之间30分钟的接触时间足以诱导凋亡,并且80%的细胞显示亚二倍体DNA含量。添加氧化剂清除剂N-乙酰半胱氨酸可抑制由硬脂胺组成的阳离子脂质体诱导的凋亡。
阳离子脂质体诱导WEHI 231细胞凋亡,并且活性氧的产生在阳离子脂质体诱导的凋亡调节中很重要。众所周知,阳离子脂质体具有细胞毒性,而凋亡可能是这种毒性的原因之一。