Inducing neutrophil recruitment in the liver of ICAM-1-deficient mice using polyethyleneimine grafted with pluronic P123 as an organ-specific carrier for transgenic ICAM-1
Inducing neutrophil recruitment in the liver of ICAM-1-deficient mice using polyethyleneimine grafted with pluronic P123 as an organ-specific carrier for transgenic ICAM-1
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DOI：
10.1038/sj.gt.3301716
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发表时间：
2002-07-01
期刊：
影响因子：
5.1
通讯作者：
Alakhov, V
中科院分区：
文献类型：
--
作者：
Ochietti, B;Lemieux, P;Alakhov, V
血管内皮表面细胞粘附分子和趋化因子的协调表达负责免疫效应细胞归巢至目标位点。将未激活的免疫细胞吸引到目标器官的一种方法是使用负责白细胞募集的转基因表达的粘附分子。我们之前已经证明，用非离子两亲性 Pluronic P123 嵌段共聚物 (P123PEI) 接枝的聚乙烯亚胺 (PEI) 可以改变质粒 DNA 向肝脏的生物分布。在本研究中，将携带编码鼠 ICAM-1 分子的基因的 P123PEI 配制的质粒静脉注射。转化为 ICAM-1 缺陷的转基因小鼠。 ICAM-1 mRNA 表达的 RT-PCR 分析表明，P123PEI 诱导肝脏中 ICAM-1 的剂量依赖性表达。此外，ICAM-1 的这种表达诱导中性粒细胞侵入肝脏，而在注射配制的对照质粒或裸 DNA 的小鼠中没有观察到这种侵入。这些结果表明，静脉注射后，P123PEI 允许肝脏中功能性转基因表达。注射，ICAM-1 可用于通过吸引免疫效应细胞来增强局部免疫反应。
Coordinated expression of cell adhesion molecules and chemokines on the surface of vascular endothelium is responsible for the homing of immune effector cells to targeted sites. One way to attract non-activated immune cells to targeted organs is to use transgenically expressed adhesion molecules responsible for leukocyte recruitment. We have previously shown that polyethyleneimine (PEI) grafted with non-ionic amphiphilic Pluronic P123 block copolymer (P123PEI) modifies biodistribution of plasmid DNA toward the liver. In the present study, a P123PEI-formulated plasmid carrying the gene encoding for the murine ICAM-1 molecule was injected i.v. into transgenic ICAM-1-deficient mice. The RT-PCR analysis of ICAM-1 mRNA expression showed that P123PEI induced a dose-dependent expression of ICAM-1 in the liver. Furthermore, this expression of ICAM-1 induced neutrophil invasion in the liver, while no such invasion was observed in mice injected with formulated control plasmid or naked DNA. These results suggest that P123PEI allows functional transgene expression in the liver following i.v. injection and that ICAM-1 could be used to enhance immune response locally by attracting immune effector cells.