ADMA对单核细胞来源的树突状细胞成熟和免疫的影响  

Effect of Asymmetrical Dimethylarginine (ADMA) on Maturation and Function of Dendritic Cells Drived from Monocyte

作　　者：徐华宝 朱伟国[2] 李闪[2] 朱建华[2] 

机构地区：[1]诸暨市人民医院,浙江诸暨311800 [2]浙江大学附属第一医院,浙江杭州310003

出　　处：《心脑血管病防治》2010年第6期428-431,408,共5页CARDIO-CEREBROVASCULAR DISEASE PREVENTION AND TREATMENT

摘　　要：目的:通过观察非对称性二甲基精氨酸(ADMA)对树突状细胞(dendritic cells,DCs)成熟及免疫的影响来探讨AS形成的可能机制。方法:贴壁法分离人外周血单核细胞,在含重组人粒-巨噬细胞集落刺激因子(rhGM-CSF 20ng/ml)和重组人白细胞介素-4(rhIL-4,10ng/ml)的完全培养基中培养,五天后收集imDC,用1、8、16umol/L的ADMA干预未成熟DC 24h。用流式细胞术检测DC细胞表面分子的表达、吞噬能力及DC的凋亡,用混合淋巴细胞反应检测成熟DC刺激T淋巴细胞增殖的能力,用ELISA检测DC细胞因子的分泌。结果:生理浓度ADMA并不刺激DC成熟及分化;但病理浓度ADMA抑制DC成熟;抑制DC诱导的T淋巴细胞增殖;诱导DC凋亡:抑制DC分泌IL-12细胞因子、TNF-α及IL-10细胞因子。结论:生理浓度ADMA并不刺激DC成熟及分化;但病理浓度AD-MA抑制DC成熟和免疫。Objective The purpose of this study is to explore the mechanism of generation and progress of AS by investigating the effect of ADMA on the expression of dendritic cells（DCs） and the interaction between DCs and T lymphocytes.Methods Immunophenotype,such as HLA-DR,CD1a,CD86 and CD83,of ADMA-treated DCs was monitored by flow cytometry.Allogeneic T cell activation by ADMA-treated DCs was tested by mixed lymphocyte reaction（MLR）.The apoptosis of ADMA-treated DCs was measured by flow cytometry using a Annexin V-FITC.The expression of IL-10,IL-12 and TNF-α on ADMA-treated DCs was detected by immunofluorescence stain.Results The majority of immature DCs cultured in control cultures with GM-CSF and IL-4 expressed high level of HLA-DR,moderate levels of CD1a and CD86,and low level of CD83,while the mature DCs exposed to LPS expressed high levels of HLA-DR,CD86 and CD83,moderate level of CD1a.The presence of ADMA did not change the phenotype of immature DCs and high concentration ADMA inhibit the maturation of DCs.Immature DCs in high concentration ADMA were less effective in stimulating T-cell proliferation.And immature DCs in high concentration ADMA were more effective to apoptosis.The expression of IL-10,IL-12 and TNF-α on DCs was significantly reduced by ADMA in a concentration-dependent manner as assessed by immunofluorescence stain.Conclusions High concentration ADMA is able to inhibit the maturatiom of DCs and promote the apoptosis of DCs.ADMA can reduce the expression of IL-10,IL-12 and TNF-α on DCs.These data indicate a novel pathophysiological mechanism for ADMA promoting atherogenesis.

关 键 词：非对称性二甲基精氨酸(ADMA) 树突状细胞(DCs) 动脉粥样硬化 体外实验 

分 类 号：R392[医药卫生—免疫学]