细胞亲环素A对单核来源泡沫细胞功能的影响  

Effect of cyclophilin A on monocyte-derived foam cells

作　　者：戎梦瑶[1] 朵瑞雪[1] 朱平[1] 王聪华[1] 汪莉[1] 樊春梅[1] 王彦宏[1] 

机构地区：[1]第四军医大学西京医院临床免疫科,陕西西安710032

出　　处：《细胞与分子免疫学杂志》2011年第5期515-518,共4页Chinese Journal of Cellular and Molecular Immunology

基　　金：国家重点基础研究发展计划(973)资助项目(2009CB521705)

摘　　要：目的：研究细胞亲环素A对单核来源泡沫细胞功能的影响,探讨细胞亲环素A（CypA）在动脉粥样硬化发病过程中的作用。方法：以氧化型低密度脂蛋白诱导,建立人单核细胞系（THP-1细胞）分化的泡沫细胞模型,采用油红O染色进行形态学鉴定。以不同浓度的重组人CyPA（50、100、200μg/L）刺激人单核来源的泡沫细胞,通过细胞黏附实验、基质侵袭实验和明胶酶谱实验检测在分化的过程中CypA作用前后,MMP的表达,细胞黏附和侵袭力的变化。进而用环孢素A（CsA）、HAb18 mAb、c7b8 f10以及HAb18 mAb联合c7b8 f10分别进行阻断实验,观察对泡沫细胞功能的抑制作用。结果：在单核向泡沫细胞分化的各阶段中,泡沫细胞MMP-2、9的表达,黏附基质和侵袭能力均较THP-1单核株和巨噬细胞显著增强（P〈0.05）;CyPA对泡沫细胞上述功能有促进作用,浓度100~200μg/L的作用效果最明显（P〈0.05）;以上拮抗剂均可不同程度阻断CypA作用于泡沫细胞前后的上调作用,其中以HAb18 mAb联合c7b8 f10的抑制作用最明显（P〈0.05）。结论：CypA上调了动脉粥样硬化泡沫细胞MMP-2、9的表达及其活性,增强了泡沫细胞黏附、侵袭能力,其促进作用可被CypA和CD147的拮抗剂所抑制。这一作用机制可能与动脉粥样硬化斑块不稳定性的发病机制相关联,并为其治疗提供了新的理论基础。AIM： To observe whether cyclophilin A（CypA）has an effect on macrophage-derived foam cells,and to investigate the involvement of CypA in the development of atherosclerosis.METHODS： The foam cell model was established through incubating the human monocyte line（THP-1 cells） with oxidized low density lipoproteins（ox-LDL）.The cells were stained with fresh oil red O to study the morphology of the macrophage-derived foam cells.The cell adhesion,invasion and the production of matrix metalloproteinase（MMPs） of the macrophage-derived foam cells were detected by adhesion assay,invasion assay and gelatin zymography respectively both in the absence or presence of different concentrations of purified CypA（50,100,200 μg/L）.Then the foam cells were respectively pre-treated with CsA,c7b8f10,HAb18 mAb,and dual treatment of c7b8f10 and HAb18 mAb respectively,to investigate the inhibitory effect on macrophage-derived foam cells.RESULTS： The adhesion,invasion and the production of MMP-9 and MMP-2 were enhanced during the differentiation of monocytes into macrophages（P0.05）.CypA,especially in the concentration of 100 ng/mL,significantly promoted the function of macrophage-derived foam cells（P0.05）.CsA,c7b8f10,HAb18 mAb,and c7b8f10-HAb18 mAb combination dramatically inhibited the function of macrophage-derived foam cells both in the absence or presence of CypA（P0.05）.The c7b8f10-HAb18 mAb combination pretreatment had the most obviously suppressive effect on macrophage-derived foam cells（P0.05）.CONCLUSION： These findings suggest that CypA up regulates the adhesion,the invasion and the expressions of MMP-2 and MMP-9 in macrophage-derived foam cells.The CypA effect is blocked by the pretreatment of the different antagonists.This research might suggest the correlation between atherosclerosis pathogenesis and the vulnerability of atherosclerotic plaques,and thus give us some good ideas for atherosclerosis therapy in future.

关 键 词：亲环素A 单核/巨噬细胞 泡沫细胞 动脉粥样硬化 

分 类 号：R392.11[医药卫生—免疫学]