UPTAKE OF LIPOSOMES BY CULTURED MOUSE BONE-MARROW MACROPHAGES - INFLUENCE OF LIPOSOME COMPOSITION AND SIZE

UPTAKE OF LIPOSOMES BY CULTURED MOUSE BONE-MARROW MACROPHAGES - INFLUENCE OF LIPOSOME COMPOSITION AND SIZE
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DOI:
10.1016/0005-2736(91)90268-d
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发表时间:
1991-01-09
期刊:
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子:
--
通讯作者:
LEE, KC
LEE, KC
中科院分区:
其他
文献类型:
--
作者:
ALLEN, TM;AUSTIN, GA;LEE, KC

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先前已经在体内检测了多种脂质体组合物影响脂质体摄取到网状内皮(RE,单核吞噬细胞)系统细胞中的能力(艾伦,T.M.和Chonn,A. 04 The Dog(1987)223,42-46;艾伦(Allen)等人(1989)生物化学(Biochim. Biophys. Acta 981,27-35)。 在这项研究中,我们研究了培养的小鼠骨髓巨噬细胞内吞各种组合物的脂质体的能力,并寻找体内和体外观察之间的相关性。 体内显著降低脂质体RE摄取的化合物,如单唾液酸神经节苷脂(G(M1))和聚乙二醇的新型合成脂质衍生物(PEG-PE),也以浓度依赖性方式大大降低骨髓巨噬细胞的脂质体摄取。 增加双层刚性的脂质,如鞘磷脂(SM)和胆固醇(CHOL),在体内和体外脂质体的摄取均降低。 同样,在含有磷脂酰丝氨酸(PS)或各种神经节苷脂的脂质体的体内行为与这些脂质体被骨髓巨噬细胞摄取的能力之间观察到正相关性。 在37 ℃下,巨噬细胞的总脂质体摄取随孵育时间增加,而在4 ℃下观察到与巨噬细胞的脂质体缔合非常少。 脂质体的摄取增加脂质体浓度和卵磷脂(PC)的摄取在40 nmol脂质每毫克细胞蛋白质的脂质体组成的。 脂质体大小与巨噬细胞的摄取呈负相关。
A wide range of liposome compositions have previously been examined in vivo for their ability to affect the uptake of liposomes into cells of the reticuloendothelial (RE, mononuclear phagocyte) system (Allen, T.M. and Chonn, A. (1987) FEBS Lett. 223, 42-46; Allen et al. (1989) Biochim. Biophys. Acta 981, 27-35). In this study we have examined the ability of cultured murine bone marrow macrophages to endocytose liposomes of various compositions and have looked for correlations between the in vivo and the in vitro observations. Compounds which substantially decreased RE uptake of liposomes in vivo, such as monosialoganglioside (G(M1)) and a novel synthetic lipid derivative of polyethyleneglycol (PEG-PE), also greatly decreased liposome uptake by bone marrow macrophages in a concentration-dependent manner. Lipids which increase bilayer rigidity, such as sphingomyelin (SM) and cholesterol (CHOL), decreased both in vivo and in vitro uptake of liposomes. Likewise, positive correlations were observed between the in vivo behavior of liposomes containing phosphatidylserine (PS) or various gangliosides and the ability of these liposomes to be taken up by bone marrow macrophages. Total liposome uptake by macrophages increased with incubation time at 37-degrees-C while very little liposome association with the macrophages was observed at 4-degrees-C. Liposome uptake increased with liposome concentration and for liposomes composed of egg phosphatidylcholine (PC) uptake plateaued at 40 nmol lipid per mg cell protein. There was an inverse correlation between liposome size of extruded large unilamellar vesicles and their uptake by macrophages.