Interaction of dendritic cells with antigen-containing liposomes: effect of bilayer composition

Interaction of dendritic cells with antigen-containing liposomes: effect of bilayer composition
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DOI:
10.1016/j.vaccine.2003.11.008
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发表时间:
2004-05-07
期刊:
影响因子:
5.5
通讯作者:
Frokjaer, S
Frokjaer, S
中科院分区:
医学3区
文献类型:
--
作者:
Foged, C;Arigita, C;Frokjaer, S

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通过利用树突细胞(DC)的有效抗原呈递特性,可以提高疫苗功效,因为近年来它们刺激特定主要组织相容性复合物限制性免疫反应的能力已得到充分证明。鉴于此,我们研究了双层组成如何影响含抗原脂质体与 DC 的相互作用。通过流式细胞术和共聚焦显微镜对单核细胞来源的人 DC 和鼠骨髓来源的 DC 在与脂质体体外孵育时进行分析和比较。在两种 DC 类型的情况下,具有磷脂酰胆碱、胆固醇和磷脂酰甘油或磷脂酰丝氨酸双层组合物的阴离子脂质体与总 DC 群体的有限部分相互作用。包含甘露糖化磷脂酰乙醇胺 (Man-PE) 来靶向甘露糖受体 (MR),增加了带负电荷的脂质体与人和鼠 DC 的相互作用。在人类 DC 中添加多糖甘露聚糖可以阻断这种增加,表明摄取可能是由甘露糖受体介导的。含有三甲基丙烷铵的阳离子脂质体与两种 DC 类型的比例非常高,并且可以在细胞内大量检测到。总之,脂质体双层成分对与 DC 的相互作用具有重要影响,并且可能对疫苗接种结果至关重要。 (C) 2003 Elsevier Ltd. 保留所有权利。
Vaccine efficacy might be improved by exploiting the potent antigen presenting properties of dendrite cells (DCs), since their ability to stimulate specific major histocompatibility complex-restricted immune responses has been well documented during the recent years. In that light, we investigated how the interaction of antigen-containing liposomes with DCs was affected by the bilayer composition. Monocyte-derived human DCs and murine bone marrow-derived DCs were analysed and compared upon in vitro incubation with liposomes by flow cytometry and confocal microscopy. Anionic liposomes with a bilayer composition of phosphatidylcholine, cholesterol and phosphatidylglycerol or phosphatidylserine interacted with a limited fraction of the total DC population in case of both DC types. Inclusion of mannosylated phosphatidylethanolamine (Man-PE) for targeting to the mannose receptor (MR) increased the interaction of negatively charged liposomes with both human and murine DCs. This increase could be blocked in human DCs by addition of the polysaccharide mannan indicating that uptake might be mediated by the mannose receptor. Cationic liposomes containing trimethyl ammonium propane interacted with a very high percentage of both DC types and could be detected in high amounts intracellularly. In conclusion, liposome bilayer composition has an important effect on interaction with DCs and might be critical for the vaccination outcome. (C) 2003 Elsevier Ltd. All rights reserved.