Modulation of murine liver macrophage clearance of liposomes by diethylstilbestrol. The effect of vesicle surface charge and a role for the complement receptor Mac-1 (CD11b/CD18) of newly recruited macrophages in liposome recognition
Modulation of murine liver macrophage clearance of liposomes by diethylstilbestrol. The effect of vesicle surface charge and a role for the complement receptor Mac-1 (CD11b/CD18) of newly recruited macrophages in liposome recognition
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DOI：
10.1016/s0168-3659(01)00481-3
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发表时间：
2002-01-17
影响因子：
10.8
通讯作者：
Patel, HM
中科院分区：
文献类型：
--
作者：
Moghimi, SM;Patel, HM
我们研究了经静脉注射的中性脂质体（卵磷脂/卵磷脂/胆固醇，摩尔比7:2）、阴离子脂质体（卵磷脂/胆固醇/二烷基磷酸，摩尔比7:2:1）和阳离子脂质体（卵磷脂/胆固醇/硬脂胺，摩尔比7:2:1）在小鼠体内的血液清除率和网状内皮器官分布，它们的大小分布大致相同。雄性小鼠腹腔注射DES，每只小鼠（体重22- 25g） 1mg，无论初始囊泡表面电荷如何，脂质体的血管清除率都有所增加。在des治疗的动物中，脂质体血管清除率的增强与肝脏重量的增加以及肝脏吞噬的增加有关。然而，与大小分布相似的中性和负电荷囊泡相比，DES处理显著增强了带正电荷的脂质体的肝隔离（以每克肝组织注射脂质体剂量的百分比为基础）。“肝阻断”实验也证实了这一观察结果，在肝阻断实验中，预先静脉注射大小分布相同的脂质体，并与试验囊泡的脂质体电荷相等，即可诱导肝阻断。体外细胞悬液研究表明，des处理小鼠的Kupffer细胞对脂质体摄取的增强（与初始囊泡表面电荷无关）与血液调理过程的变化无关。此外，体外研究还表明，在DES治疗后，不同的肝巨噬细胞（常驻细胞和募集细胞）参与脂质体识别的多种机制。例如，在des治疗的动物中，新招募的肝巨噬细胞被发现在通过补体受体（Mac-1）清除硬脂胺结合脂质体中发挥重要作用。常驻Kupffer细胞似乎通过其他受体识别阳离子囊泡，因为在这些细胞中几乎没有Mac-1的表达。另一方面，补体受体似乎在des处理小鼠肝巨噬细胞对阴离子DCP囊泡的摄取中起次要作用。DES似乎为剖析脂质体-巨噬细胞相互作用的机制提供了一种新的方法。(C) 2002 Elsevier Science B.V.版权所有
We have studied the blood clearance and reticuloendothelial organ distribution of intravenously injected neutral (egg phosphatidylcholine, egg PC/cholesterol, mol ratio 7:2), anionic (egg PC/cholesterol/dicetylphosphate, mol ratio 7:2:1), and cationic (egg PC/cholesterol/stearylamine, mol ratio 7:2:1) liposomes of approximately the same size distribution in mice 3 days after treatment with the synthetic oestrogen diethylstilbestrol (DES). Male mice administered DES intraperitoneally at a dose of 1 mg per mouse (body weight 22-25 g) manifested an increase in the vascular clearance rate of liposomes irrespective of the initial vesicle surface charge. The enhancement in the vascular clearance of liposomes in DES-treated animals was associated with a concomitant increase in liver weight as well as hepatic phagocytosis. However, DES treatment significantly enhanced the hepatic sequestration (on the basis of % of injected dose of liposomes per g of liver tissue) of positively charged liposomes when compared to both neutral and negatively charged vesicles of similar size distribution. This observation was also confirmed by the 'hepatic-blockade' experiments where blockade was induced by prior intravenous injection of liposomes of the same size distribution and charge to that of test vesicles. The in vitro cell suspension studies suggested that the enhanced liposome uptake (irrespective of the initial vesicle surface charge) by Kupffer cells of DES-treated mice was independent of changes in the blood opsonization processes. Furthermore, in vitro studies also showed the operation of multiple mechanisms and involvement of different populations of liver macrophages (resident and recruited cells) in liposome recognition following DES treatment. For example, in DES-treated animals, the newly recruited liver macrophages were found to play a major role in the clearance of stearylamine incorporated liposomes via complement receptors (Mac-1). The resident Kupffer cells seem to recognize cationic vesicles via other receptors as the expression of Mac-1 is virtually absent in these cells. On the other hand, complement receptors seem to play a minor role in the uptake of anionic DCP vesicles by hepatic macrophages of DES-treated mice. DES appears to offer a new approach in dissecting the mechanisms of liposome-macrophage interaction. (C) 2002 Elsevier Science B.V. All rights reserved.