中山醫學大學機構典藏 CSMUIR:Item 310902500/7125
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    jsp.display-item.identifier=請使用永久網址來引用或連結此文件: https://ir.csmu.edu.tw:8080/ir/handle/310902500/7125


    题名: 人類微小病毒B19結構蛋白獨立區域VP1u在誘發自體免疫反應之功能與分子機制探討　（新制多年期第1年）
    作者: 徐再靜
    贡献者: 中山醫學大學微生物免疫研究所
    日期: 2009
    上传时间: 2013-12-23T09:33:43Z (UTC)
    摘要: 在我們最近發表的研究結果顯示急性感染人類微小病毒B19 (Human Parvovirus B19, B19)的病
    人血清中之抗牛心脂抗體和抗β2GPI抗體(抗磷脂質抗體)的表現可能和B19 結構蛋白獨立區域
    (VP1u)有關。因此推測VP1u 在B19 感染、自體免疫和自體抗體(ex:抗磷脂質抗體)產生之間可
    能扮演著相當重要的角色。於是我們進一步將抗B19-VP1u 抗體以靜脈注射方式至正常BALB/c
    老鼠體內﹐則發現會誘發抗B19 -VP1u 抗體﹐抗磷脂質抗體﹐及導致BALB/c 小鼠血小板下降
    和血液凝固時間(aPTT)延長。另外﹐我們也發現抗B19-VP1u 抗體﹐如同人類的抗磷脂質抗體和
    抗β2GPI抗體﹐會促進內皮細胞活化。而為了更進一步了解VP1u 引發自體免疫之相關機轉，
    我們探討(1)VP1u 對老鼠巨噬細胞Raw264.7 的影響，首先證明重組蛋白B19-VP1u 具有sPLA2
    活性﹐並發現此sPLA2 的活性會影響老鼠巨噬細胞Raw264.7 之遷移、吞噬、相關發炎細胞激
    素(IL-6、IL-1β)及MMP9 mRNA 的表現增加。此外，也發現sPLA2 活性會促進磷酸化ERK1/2
    和磷酸化JNK 蛋白質表現增加。另外，為了了解抗B19-VP1u 抗體在免疫疾病個體之角色，我
    們將抗B19-VP1u 抗體以靜脈注射方式至狼瘡小鼠體內﹐發現會誘發抗B19 VP1u 抗體﹐抗磷脂
    質抗體和抗dsDNA 抗體的表現，及導致狼瘡小鼠血小板下降和血液凝固時間(aPTT)延長。此外
    也發現施打抗B19-VP1u 抗體之狼瘡小鼠肝臟的MMP9 活性及MMP9 蛋白質表現均有顯著增
    加，並且透過磷酸化PI3K 和ERK 蛋白質之機轉。以上這些研究結果將可提供一些線索在
    B19-VP1u 及抗B19-VP1u 抗體與自體免疫的相關研究。
    In our recent studies, increased anti-cardiolipin and beta-2GPI antibodies were detected in sera from
    patients with acute B19 infection (IgM+/IgG+/DNA+). Consistently, the induction of
    anti-phospholipid and anti-cardiolipin antibodies, prolonged aPTT, and thrombocytopenia was
    observed in BALB/c mice receiving anti-B19 VP1u IgG intravenously. Additionally, we also
    demonstrated the sPLA2 activity of B19-VP1u protein and the activation of endothelial cells by
    B19-VP1u IgG as well as the results of human anti-phospholipid antibodies (anti-cardiolipin antibody
    or anti-2GPI antibody) as reported in patients with APS. In this study, we found that increased
    migration, phagocytic index, and mRNA expressions of pro-inflammatory cytokines (IL-6, IL-1) and
    MMP-9 were observed in RAW264.7 cells treated with B19-VP1u proteins that had sPLA2 activity.
    Moreover, significant reduction of platelet count and prolonged thrombocytopenia time were detected
    in anti-B19-VP1u IgG group as compared to other groups, whereas significant increases of
    anti-B19-VP1u, anti-phospholipid (APhL), and anti-dsDNA antibody binding activity were detected in
    anti-B19-VP1u group. Additionally, significant increases of MMP9 activity and protein expression
    were detected in B19-VP1u IgG group. Notably, phosphatidylinositol 3-phosphate kinase (PI3K) and
    phosphorylated extracellular signal-regulated kinase (ERK) proteins were involved in the induction of
    MMP9. These findings could provide clues in understanding the role of B19-VP1u and in B19
    infection and B19-related diseases.
    URI: https://ir.csmu.edu.tw:8080/ir/handle/310902500/7125
    显示于类别:[免疫學研究所] 研究計劃

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