RECOGNITION OF LIPOSOMES BY CELLS - INVITRO BINDING AND ENDOCYTOSIS MEDIATED BY SPECIFIC LIPID HEADGROUPS AND SURFACE-CHARGE DENSITY
RECOGNITION OF LIPOSOMES BY CELLS - INVITRO BINDING AND ENDOCYTOSIS MEDIATED BY SPECIFIC LIPID HEADGROUPS AND SURFACE-CHARGE DENSITY
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DOI：
10.1016/0005-2736(92)90086-2
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发表时间：
1992-01-31
期刊：
影响因子：
--
通讯作者：
PAPAHADJOPOULOS, D
中科院分区：
文献类型：
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作者：
LEE, KD;HONG, K;PAPAHADJOPOULOS, D
我们研究了不同表面性质的脂质体与两种哺乳动物细胞系，CV1，非洲绿色猴肾细胞系，和J774，小鼠巨噬细胞样细胞系的相互作用。 使用脂质体包封的pH敏感性荧光染料吡喃和脂质标记物罗丹明-PE，通过荧光测定法定量脂质体的细胞表面结合和内吞作用。 脂质体的摄取依赖于脂质体的表面性质和细胞系。 卵磷脂（PC）/胆固醇（C）（2：1）脂质体中掺入的带负电荷的磷脂被两种细胞系不同程度地识别，这取决于脂质体双层中的脂质头基及其电荷密度。 包含9%的磷脂酰丝氨酸（PS），磷脂酰甘油（PG），或磷脂酸（PA）促进CV1细胞的摄取超过20倍。 将这些带负电荷的脂质的含量增加超过9%不会进一步增强摄取。 相反，9%的单唾液酸神经节苷脂G（M1），磷脂酰肌醇（PI），或磷脂酰乙醇胺共轭聚乙二醇（PEG-PE）没有促进摄取。 在PC/C脂质体中加入9%PS、PG、PA或PI并不能增强J774细胞的摄取，但当这些阴离子脂质的浓度增加时，观察到了急剧的增强。 至少需要50%的PS、PG或PI才能达到CV1细胞的摄取水平。 聚阴离子是清道夫受体的竞争性配体，可抑制J774细胞对含50%PS的脂质体的摄取，但不抑制CV1的摄取。 从不同的摄取模式和与各种聚阴离子的竞争，这两种细胞系的脂质体摄取不同的机制建议。 在具有不同脂质组成的脂质体的摄取速率中观察到的差异似乎主要是由于脂质体和细胞膜组分之间的结合差异。 各种脂质体与这些细胞系，特别是CV1细胞的体外相互作用显示出与脂质体的体内清除率的显著相似性。
We investigated the interaction of liposomes of different surface properties with two mammalian cell lines, CV1, an African green monkey kidney cell line, and J774, a murine macrophage-like cell line. Cell surface binding and endocytosis of liposomes were quantified by fluorometry, using the liposome-encapsulated pH-sensitive fluorescent dye, pyranine, and the lipid marker rhodamine-PE. The liposome uptake was dependent both on the surface properties of the liposomes and on the cell line. Negatively charged phospholipids incorporated into egg phosphatidylcholine (PC)/cholesterol (C) (2:1) liposomes were recognized by the two cell lines to different extents depending on the lipid headgroup and its charge density in the liposome bilayer. Inclusion of 9% phosphatidylserine (PS), phosphatidylglycerol (PG), or phosphatidic acid (PA) promoted the uptake by CV1 cells more than 20-fold. Increasing the content of these negatively charged lipids beyond 9% did not further enhance the uptake. In contrast, 9% monosialoganglioside G(M1), phosphatidylinositol (PI), or phosphatidylethanolamine conjugated to poly(ethylene glycol) (PEG-PE) did not promote the uptake. Inclusion of 9% PS, PG, PA or PI in PC/C liposomes did not enhance the uptake by J774 cells, but a drastic enhancement was observed when increasing concentrations of these anionic lipids were incorporated in the liposome bilayer. At least 50% PS, PG, or PI was needed to reach the level of uptake seen with CV1 cells. The uptake of liposomes containing 50% PS by J774 cells was inhibited by poly-anions which are the competing ligands for scavenger receptors, but the uptake by CV1 was not inhibited. Different mechanisms of liposome uptake by these two cell lines are suggested from the different patterns of uptake and the competition with various poly-anions. The differences observed in the uptake rate of liposomes with different lipid compositions seemed to be primarily due to the differences in the binding between liposomes and cell membrane components. The in vitro interaction of various liposomes with these cell lines, especially CV1 cells, shows significant similarities to the in vivo clearance rates of the liposomes.