Anti-endothelial cell antibody and thrombosis

抗内皮细胞抗体与血栓形成

• 批准号: 13670444
• 负责人: HIRABAYASHI Yasuhiko
• 金额: $ 2.62万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670444/
• 关键词: thrombosis; recurrent abortion; endothelial cell; autoantibody; anti-polysaccharide antibody; 自己拡体; 接着因子

1. A heparin-like pentasaccharide structure, termed vascular pentasaccharide (VPS), on the surface of endothelial cells(EC) contributes to anticoagulation in the circulation through the binding to antithrombin III(ATIII). We developed a simple and sensitive ELISA to detect anti-VPS antibodies in sera. Anti-VPS antibodies were detected in 18(20.9%) of 86patients with thrombisis, 14(46.7%) of 34 with recurrent abortion, and 3(2.7%) of III with no history of thrombotic of episodes. Among 32 anti-VPS positive patients, 12 were diagnosed antihospholopid antibody syndrome(APS). Eight of 18 anti-VPS-positive patients with thrombosis, and 12 of 14 anti-VPS-positive patients with recurrent abortin showed negative tests for anti-phospholipid antibody(aPL) including anti-cardiolipin antibody, lupus anticoagulant or anri-prothrombin antibody. We developed were hybridoma producing anti-VPS antibody. Both serum and human monoclonal anti-VPS antbodies showed a fine specificity to VPS (ATIII binding site) and EC, but not to cardioripin, β2-glycoprotein or DNA. Administration of were monoclonal anti VPS antibody to pregnant mice failed to cause spontaneous abortion, but, caused the elevation of thrombin-antithtombin levels in the mice. These results indicate to APS. The detection of anti-VPS antibodies can contribute to the diagnosis of autoimmune thrombosis or abortion.2. (1)Serum and monoclonal anti VPS antibodies had an ability to bind human umbilical vascular endothelial cells(HUVEC), resulting in causing, the expression of CD62P and enhancing HUVEC binding of T cells.

1.内皮细胞（EC）表面上的肝素样五糖结构（称为血管五糖（VPS））通过与抗凝血酶III（ATIII）结合有助于循环中的抗凝作用。我们建立了一种简便、灵敏的ELISA检测血清中抗VPS抗体的方法。86例血栓形成患者中18例（20.9%）、34例复发性流产患者中14例（46.7%）和3例无血栓史的III型患者（2.7%）检测到抗VPS抗体。32例抗VPS阳性患者中12例诊断为抗磷脂抗体综合征（APS）。18例抗VPS阳性的血栓形成患者中有8例抗VPS阳性，14例抗VPS阳性的反复流产患者中有12例抗磷脂抗体（aPL）检测阴性，包括抗心磷脂抗体、狼疮抗凝剂或抗凝血酶原抗体。我们研制了产生抗VPS抗体的杂交瘤。血清和人源抗VPS抗体对VPS（ATIII结合位点）和EC具有良好的特异性，而对心磷脂、β2-糖蛋白和DNA无特异性。给孕鼠注射抗VPS单克隆抗体，未引起自然流产，但引起凝血酶-抗凝血酶水平升高。这些结果对APS具有指导意义。抗VPS抗体的检测有助于自身免疫性血栓形成或流产的诊断.（1）抗VPS单克隆抗体和血清均能与人脐静脉内皮细胞（HUVEC）结合，导致T细胞表达CD 62 P，增强HUVEC与T细胞的结合。

项目成果

Y.Fu, K.K.Ishii, T.Sasaki, et al.: "Regulation of human TNF αpromoter by parvovirus B19 NSI through activation of AP-1 and AP-2"J. Virology.. 76. 5395-5403 (2002)

Y.Fu、K.K.Ishii、T.Sasaki 等人：“细小病毒 B19 NSI 通过 AP-1 和 AP-2 的激活调节人 TNF α 启动子”J. 76. 5395-5403 (2002)

M.Rahman, Y.Hirabayashi, ほか: "Prednisolone Sodium Succinate Down-Regulates BSAP/Pax5 and Causes a Growth Arrest in the Nalm6 Pre-B Cell Line"Tohoku J. Exp. Med.. 193. 237-244 (2001)

M.Rahman、Y.Hirabayashi 等人：“泼尼松龙琥珀酸钠下调 BSAP/Pax5 并导致 Nalm6 Pre-B 细胞系生长停滞”Tohoku J. Exp. 193. 237-244（ 2001）

M.Rhaman, Y.Hirabayashi, et al.: "A repressor element in the 5' untranslated region of human Pax 5 exion 1A."Gene. 263. 59-66 (2001)

M.Rhaman、Y.Hirabayashi 等人：“人 Pax 5 外显子 1A 5 非翻译区中的阻遏元件。”基因。

T.Suzuki, Y.Hirabayashi, et al.: "Human parvovirus B19 infection during the inactive stage of systemic lupus erythematosus"Internal.Medicine.. (In press). (2003)

T.Suzuki、Y.Hirabayashi 等人：“系统性红斑狼疮非活动期的人类细小病毒 B19 感染”Internal.Medicine..（正在出版）。

H.Harigae, R.Ichinohasama, Kameoka ほか: "Primary marginal zone lymphoma of the thymus accompanied by chromosomalanomaly, 46X, dup(X) (p11p22)"Cancer Genetics cytogenetics. (発表予定). (2002)

H.Harigae、R.Ichinohasama、Kameoka 等：“胸腺原发边缘区淋巴瘤伴有染色体异常，46X，dup(X) (p11p22)”癌症遗传学细胞遗传学（即将出版）。