t-PA对EAE 病理性淋巴细胞与血脑屏障粘附的影响 |
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引用本文: | 王菁华,张建华,于瑞洪,穆莉莉,刘玉梅,刘传亮,王广友.t-PA对EAE 病理性淋巴细胞与血脑屏障粘附的影响[J].现代生物医学进展,2015,15(27):5208-5211. |
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作者姓名: | 王菁华 张建华 于瑞洪 穆莉莉 刘玉梅 刘传亮 王广友 |
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作者单位: | 哈尔滨医科大学神经生物学教研室哈尔滨医科大学神经生物学省重点实验室 |
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基金项目: | 黑龙江省教育厅科学技术研究项目(12521208) |
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摘 要: | 目的:研究组织型纤溶酶原激活剂(t-PA)对实验性自身免疫性脑脊髓炎(EAE)小鼠病理性淋巴细胞与血脑屏障粘附的影
响。方法:用MOG35-55 肽段免疫C57BL/6小鼠建立EAE 动物模型,于发病高峰期取淋巴细胞用MOG35-55 肽段进行刺激得到
抗原特异性T淋巴细胞。通过尾静脉给予t-PA 的方法对EAE 小鼠进行干预,临床评分评价小鼠的发病情况。体外培养小鼠血脑
屏障内皮细胞系bEnd.3,应用不同浓度的t-PA 进行处理。用荧光标记MOG35-55 特异性T 细胞进行细胞粘附实验,用Transwell
小室建立体外血脑屏障模型进行细胞迁移实验。用免疫荧光化学方法检测ICAM-1 的表达情况。结果:t-PA处理可以使血脑屏障
内皮细胞与T 淋巴细胞粘附和迁移作用增强。在体外细胞培养模型中检测到t-PA诱导ICAM-1 表达升高。经过t-PA 处理的小
鼠,其血管内皮表面ICAM-1 的表达也有所上升。经t-PA 处理的EAE 小鼠发病高峰提前,症状加重。结论:t-PA 处理可以使EAE
病理性淋巴细胞与血脑屏障内皮的粘附性增加,浸润能力增强;t-PA 所引起的粘附性增加可能与bEnd.3 表面ICAM-1表达升高
有关。
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关 键 词: | 组织型纤溶酶原激活剂 实验性自身免疫性脑脊髓炎 血脑屏障 粘附 |
Effect of t-PA on Adhesion of Lymphocyte Blood-brain
Barrier Endothelium in Experimental Autoimmune
Encephalomyelitis Mice |
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Abstract: | Objective:To investigate the effects of tissue-type plasminogen activator (t-PA) on T cell-brain microvascular
endothelial cell adhesionin experimental autoimmune encephalomyelitis (EAE) mice.Methods:EAE was induced in C57BL/6 mice with
immunization of MOG35-55 peptides. T cells were obtained from lymph nodes of EAE mice 15 d after immunization, and then
stimulated with MOG35-55 peptides to obtain the MOG specific T cells. t-PA administration was performed via tail vein injections,
animals were monitored for signs of disease and were scored. Mouse brain-derived endothelial cell line, bEnd3, was treated with various
concentrations of t-PA. MOG specific T cells were labeled with Calcein AM to perform the adhesion assay. Transwell was used as the
blood-brain barrier model to perform the cell Migration assay. Immunofluorescence was performed to detect the expression of ICAM-1.Results:In the presence of t-PA, enhanced adhesion and migration of T cells to bEnd.3 cells was observed. t-PA administration can
induce ICAM-1 expression in mouse cerebral microvascular endothelial cells in vitro. Administration of t-PA in mice was also associated
with an increase in ICAM-1 expression by brain endothelial cells. By using an EAE mouse model, t-PA treatment leads to the early onset
of EAE and increased disease severity.Conclusion:t-PA administration can enhance adhesion of T cells to bEnd.3 cells which may
associate with the increase in ICAM-1 expression on brain endothelial cells by t-PA. |
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Keywords: | Tissue-type plasminogen activator Experimental autoimmune encephalomyelitis Blood brain barrier Adhesion |
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