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《Chinese Journal of Pathophysiology》 2006-10
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Foam cells can be induced by oxidized low density lipoprotein in human monocyte-derived dendritic cells

LIANG Chun~1,LUO Yu-kun~2,HUANG Dong~2,JIA Qing-zhe~2,XU Cong-feng~2,WANG Ke-qiang~2,WU Zong-gui~1,GE Jun-bo~2(~1Department of Cardiology,Changzheng Hospital,The Second Military Medical University,Shanghai 200003,China;~2 Shanghai Institute of Cardiovascular Disease,Zhongshan Hospital,Fudan University,Shanghai 200032,China)  
AIM: The purpose of this study is to investigate the mechanisms related to oxidized low-density lipoprotein(ox-LDL) and dendritic cells(DCs) in the process of atherosclerosis.METHODS: Human DCs were prepared from human CD14~+ peripheral blood monocytes using rhGM-CSF((100 μg/L)) and rhIL-4(40 μg/L).Cells were incubated with(100 mg/L) native or oxidized LDL for 72 h.The formation of foam cells was investigated by electron microscopy and oil red O staining.Phenotypic and immune functional assays were used with FACS,FITC-dextran phagocytosis,allogeneic mixed T lymphocytes reaction and secretion of Th1/Th2(IL-12/IL-2) cytokines were also conduced.RESULTS: DCs treated with ox-LDL,but not native LDL were induced into foam cells after cultured for 72 h.Compared with native LDL,ox-LDL-treated DCs were less potent in FITC-dextran phagocytosis.ox-LDL promoted allogeneic T cells proliferation.Moreover,ox-LDL upregulated CD80(72.4± 9.6 vs 89.5±10.1,P0.01),CD86(67.2±8.8 vs 80.2±11.6,P0.01), HLA-DR(80.6±9.8 vs 86.6±10.8,P0.01) and CD1a(40.2±10.3 vs 60.2±9.3,(P0.01)) expressions,increased IL-12 secretion [(44.3±8.9)ng/L vs(65.1±10.4)ng/L,P0.05] in DCs.However,the secretion of IL-2 was decreased [(43.6±7.8)ng/L vs(10.0±4.5)ng/L,P0.01] significently.CONCLUSION: DCs were induced into foam cells by ingesting ox-LDL with some functional characteristic of mature DC.DCs seem to be a new source of foam cells and play a key role in immunopathogenesis of atherosclerosis.
【Fund】: 国家重点基础研究发展规划资助项目(No.G2000056903);; 上海市科委资助项目(No.02JC14026)
【CateGory Index】: R363
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