粘附分子CD146在系统性血管炎临床和发病机制中意义的研究
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摘要
背景
系统性血管炎的靶器官是全身各级血管，血管内皮细胞的损伤、外周血白细胞的激活以及粘附分子表达的改变是其发病机制中重要的一环。研究发现，ICAM-1、CD11／CD18等粘附分子与系统性血管炎等各种免疫性疾病病情活动相关。抗CD11／CD18、ICAM-1等粘附分子的单克隆抗体已应用于免疫性疾病的临床实验，结果显示能阻断粘附分子的异常激活，从而改善病情。CD146是血管内皮细胞一个新的粘附分子，具有粘附和信号传导作用。中国科学院生物物理研究所生物大分子国家重点实验室已研制出针对CD146抗原的单克隆抗体AA98，具有明显的抑制血管内皮细胞生长和肿瘤进展的特性，也许间接反映了CD146具有促进内皮细胞增殖和血管新生的作用，因此它可能参与了各种疾病导致的内皮细胞激活和损伤。近年来，将CD146单抗包被免疫微球分离循环内皮细胞(CECs)已成为研究CECs与疾病关系的最常用的技术，研究发现系统性小血管炎活动期CECs明显增多，可以作为诊断和监测疾病活动的新标志。文献报道慢性肾功能不全(CRF)、不卧床腹膜透析和肾病综合征患者血清可溶性CD146水平明显升高，与肾脏中小血管内皮的表达增强一致，反应了广泛的内皮细胞连接区的异常。类风湿关节炎(RA)滑液中可溶性CD146升高，且与RA滑膜组织新生血管形成有关。另有报道激活的T淋巴细胞也表达CD146。这提示，CD146不但是内皮细胞表面富有活性的一个粘附分子，或许也与激活T淋巴细胞的迁移、渗出和／或归巢有关，因此可能在免疫反应尤其是血管炎发病机制中起重要的作用。
目的
研究CD146在系统性血管炎和系统性红斑狼疮(SLE)患者的血浆、外周血白细胞、肾脏及血管壁的表达情况，观察其在临床活动期和缓解期的动态变化，并分析其与临床炎症指标的相关性，探讨其在系统性血管炎发病机制中的可能作用。
Background
The targets of systemic vasculitis are all types of blood vessels.Dysfunction of vascular endothelial cell and activation of leucocytes all correlate with activation of adhesion molecules(AMs).So they are important in the pathogenesis of vasculitis. AMs such as ICAM-1 and CD 11/CD 18 corralete with disease activity in vasculitis.anti-CD11/CD 18 and anti-ICAM-1 monoclonal antibody have been used in clinical trials for autoimmune diseases and show exciting effects such as block AMs and improve clinical manifestations.Recently,studies on meaning of circulating endothelial cells(CECs) in diseases have increased in all kind of fields.One finding is that CECs increase significantly in active systemic small vasculitis and can serve as a new marker in disease activity. CD 146 is a new AMs of EC.But its role in the activation of EC is not clear. AA98,a momoclonal antibody to CD146,has been raised by Chinese Academy of Science,Center of Molecular Biology.It shows prominent abilities to inhibit proliferation and migration of HUVECs ,angiogenesis and tumor growth. So CD 146 may be involved in angiogenesis. It is reported that soluble CD146(sCD146) is increased in CRF and NS ,and correlate with dysfunction of EC.Elevated sCD146 is associated with increased expression of CD 146 in kidney.It has also been reported that sCD146 in synovial fluid of Rheumatoid Arthritis is also increased and correlate with angiogenesis of synovium.Another report is that activated T lymphocytes express CD146.We deduce that CD146 is not only a active AMs of EC,but also probably participate in the activation and migration of T lymphacytes and take part in the pathogenesis of inflammation especially vasculitis.
Objective
系统性血管炎的靶器官是全身各级血管，血管内皮细胞的损伤、外周血白细胞的激活以及粘附分子表达的改变是其发病机制中重要的一环。研究发现，ICAM-1、CD11／CD18等粘附分子与系统性血管炎等各种免疫性疾病病情活动相关。抗CD11／CD18、ICAM-1等粘附分子的单克隆抗体已应用于免疫性疾病的临床实验，结果显示能阻断粘附分子的异常激活，从而改善病情。CD146是血管内皮细胞一个新的粘附分子，具有粘附和信号传导作用。中国科学院生物物理研究所生物大分子国家重点实验室已研制出针对CD146抗原的单克隆抗体AA98，具有明显的抑制血管内皮细胞生长和肿瘤进展的特性，也许间接反映了CD146具有促进内皮细胞增殖和血管新生的作用，因此它可能参与了各种疾病导致的内皮细胞激活和损伤。近年来，将CD146单抗包被免疫微球分离循环内皮细胞(CECs)已成为研究CECs与疾病关系的最常用的技术，研究发现系统性小血管炎活动期CECs明显增多，可以作为诊断和监测疾病活动的新标志。文献报道慢性肾功能不全(CRF)、不卧床腹膜透析和肾病综合征患者血清可溶性CD146水平明显升高，与肾脏中小血管内皮的表达增强一致，反应了广泛的内皮细胞连接区的异常。类风湿关节炎(RA)滑液中可溶性CD146升高，且与RA滑膜组织新生血管形成有关。另有报道激活的T淋巴细胞也表达CD146。这提示，CD146不但是内皮细胞表面富有活性的一个粘附分子，或许也与激活T淋巴细胞的迁移、渗出和／或归巢有关，因此可能在免疫反应尤其是血管炎发病机制中起重要的作用。
目的
研究CD146在系统性血管炎和系统性红斑狼疮(SLE)患者的血浆、外周血白细胞、肾脏及血管壁的表达情况，观察其在临床活动期和缓解期的动态变化，并分析其与临床炎症指标的相关性，探讨其在系统性血管炎发病机制中的可能作用。
Background
The targets of systemic vasculitis are all types of blood vessels.Dysfunction of vascular endothelial cell and activation of leucocytes all correlate with activation of adhesion molecules(AMs).So they are important in the pathogenesis of vasculitis. AMs such as ICAM-1 and CD 11/CD 18 corralete with disease activity in vasculitis.anti-CD11/CD 18 and anti-ICAM-1 monoclonal antibody have been used in clinical trials for autoimmune diseases and show exciting effects such as block AMs and improve clinical manifestations.Recently,studies on meaning of circulating endothelial cells(CECs) in diseases have increased in all kind of fields.One finding is that CECs increase significantly in active systemic small vasculitis and can serve as a new marker in disease activity. CD 146 is a new AMs of EC.But its role in the activation of EC is not clear. AA98,a momoclonal antibody to CD146,has been raised by Chinese Academy of Science,Center of Molecular Biology.It shows prominent abilities to inhibit proliferation and migration of HUVECs ,angiogenesis and tumor growth. So CD 146 may be involved in angiogenesis. It is reported that soluble CD146(sCD146) is increased in CRF and NS ,and correlate with dysfunction of EC.Elevated sCD146 is associated with increased expression of CD 146 in kidney.It has also been reported that sCD146 in synovial fluid of Rheumatoid Arthritis is also increased and correlate with angiogenesis of synovium.Another report is that activated T lymphocytes express CD146.We deduce that CD146 is not only a active AMs of EC,but also probably participate in the activation and migration of T lymphacytes and take part in the pathogenesis of inflammation especially vasculitis.
Objective
引文
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