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].,2015,15(27):5208-5211 |
t-PA对EAE 病理性淋巴细胞与血脑屏障粘附的影响 |
Effect of t-PA on Adhesion of Lymphocyte Blood-brainBarrier Endothelium in Experimental AutoimmuneEncephalomyelitis Mice |
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DOI: |
中文关键词: 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 |
英文关键词: Tissue-type plasminogen activator Experimental autoimmune encephalomyelitis Blood brain barrier Adhesion |
基金项目:黑龙江省教育厅科学技术研究项目(12521208) |
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中文摘要: |
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。 |
英文摘要: |
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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