High expression of antioxidant proteins in dendritic cells - Possible implications in atherosclerosis
High expression of antioxidant proteins in dendritic cells - Possible implications in atherosclerosis
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DOI：
10.1074/mcp.m500262-mcp200
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发表时间：
2006-04-01
影响因子：
7
通讯作者：
Servet-Delprat, C
中科院分区：
文献类型：
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作者：
Rivollier, A;Perrin-Cocon, L;Servet-Delprat, C
树突状细胞(DC)在DC-T细胞同种异体反应中表现出激活初始T细胞和启动初始T细胞反应的独特能力。分散控制系统经常在压力条件下运行。氧化应激可促进DC产生炎性细胞因子。我们进行了蛋白质组学分析，以了解在DC分化和成熟过程中，在蛋白质表达水平上发生了哪些主要变化。对单核细胞、未成熟树突状细胞和成熟树突状细胞进行比较二维凝胶分析。在成熟DC阶段，锰超氧化物歧化酶(Mn-SOD)占凝胶展示蛋白的0.7%。这一重要数量的锰-超氧化物歧化酶是对抗超氧阴离子自由基的主要抗氧化防御系统，但其产物过氧化氢对细胞也是有害的。过氧化还蛋白(PRX)酶在清除这种过氧化作用中起着重要作用。在DC分化成熟过程中，Prx1的表达水平持续升高，Prx6的表达水平持续下降，Prx2在未成熟的DC阶段达到峰值。因此，DC比单核细胞更能抵抗含有有毒有机过氧化物和过氧化氢的大量氧化型低密度脂蛋白诱导的细胞凋亡。此外，DC刺激的T细胞产生高水平的核因子kappa B配体受体激活物，这是单核细胞和DC的趋化和生存因子。这项研究深入了解了DC最初表达非常高水平的抗氧化酶如Mn-SOD和PRX1，解毒氧化的低密度脂蛋白，以及通过它们激活的T细胞诱导高水平的核因子kappa B配体受体激活物的能力，并进一步强调了DC在动脉粥样硬化中可能发挥的作用，这种病理被认为是一种慢性炎症性疾病。
Dendritic cells (DCs) display the unique ability to activate naive T cells and to initiate primary T cell responses revealed in DC-T cell alloreactions. DCs frequently operate under stress conditions. Oxidative stress enhances the production of inflammatory cytokines by DCs. We performed a proteomic analysis to see which major changes occur, at the protein expression level, during DC differentiation and maturation. Comparative two-dimensional gel analysis of the monocyte, immature DC, and mature DC stages was performed. Manganese superoxide dismutase (Mn-SOD) reached 0.7% of the gel-displayed proteins at the mature DC stage. This important amount of Mn-SOD is a primary antioxidant defense system against superoxide radicals, but its product, H2O2, is also deleterious for cells. Peroxiredoxin (Prx) enzymes play an important role in eliminating such peroxide. Prx1 expression level continuously increased during DC differentiation and maturation, whereas Prx6 continuously decreased, and Prx2 peaked at the immature DC stage. As a consequence, DCs were more resistant than monocytes to apoptosis induced by high amounts of oxidized low density lipoproteins containing toxic organic peroxides and hydrogen peroxide. Furthermore DC-stimulated T cells produced high levels of receptor activator of nuclear factor kappa B ligand, a chemotactic and survival factor for monocytes and DCs. This study provides insights into the original ability of DCs to express very high levels of antioxidant enzymes such as Mn-SOD and Prx1, to detoxify oxidized low density lipoproteins, and to induce high levels of receptor activator of nuclear factor kappa B ligand by the T cells they activate and further emphasizes the role that DCs might play in atherosclerosis, a pathology recognized as a chronic inflammatory disorder.