Forum original research communication - Heme oxygenase-1 ameliorates ischemia/reperfusion injury by targeting dendritic cell maturation and migration
Forum original research communication - Heme oxygenase-1 ameliorates ischemia/reperfusion injury by targeting dendritic cell maturation and migration
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DOI：
10.1089/ars.2007.1801
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发表时间：
2007-12-01
影响因子：
6.6
通讯作者：
Volk, Hans-Dieter
中科院分区：
文献类型：
--
作者：
Kotsch, Katja;Martins, Paulo N. A.;Volk, Hans-Dieter
缺血/再灌注损伤（IRI）通过增加移植物免疫原性对短期和长期肾移植物存活率产生重大影响。通过诱导血红素加氧酶1（HO-1）进行供体预处理已被证明对移植物具有细胞保护和抗炎作用，从而导致移植物免疫原性降低。本研究分析了HO-1介导的细胞保护作用在冷保存大鼠移植肾中的作用及其机制。我们使用定制的cDNA微阵列研究了短期或长期冷缺血后同种异体移植物的差异基因表达模式。长时间的冷缺血导致，12小时后植入，增强水平的粘附分子，热休克蛋白，趋化因子（CXCL 10），和一个显着的上调免疫蛋白酶体。接下来，我们解决了在器官供体中诱导HO-1或其副产物一氧化碳（CO）是否靶向与增强的免疫原性相关的这些候选标志物的问题。诱导HO-1或CO在器官供体器官摘取前24小时导致受体脾脏中免疫蛋白酶体，MHC II类表达和共刺激分子的mRNA水平降低，表明供体树突状细胞的迁移和活化减少。这一观察结果表明，HO-1/CO诱导通过抑制供体来源的树突状细胞的免疫原性来保护边缘同种异体移植物。
Ischemia/reperfusion injury (IRI) has a major impact on short- and long-term renal allograft survival by increasing graft immunogenicity. Donor preconditioning by inducing heme oxygenase 1 (HO-1) has been proven to exert cytoprotective and antiinflammatory effects on the graft, thus resulting in reduced graft immunogenicity. The study analyzed the effects and mechanisms of HO-1-mediated cytoprotection in rat kidney transplants exposed to cold preservation. We studied the differential gene-expression patterns of allografts after either short or long cold ischemia using a customized cDNA microarray. Prolonged cold ischemia led, 12 h after engraftment, to enhanced levels of adhesion molecules, heat-shock proteins, chemokines (CXCL10), and a remarkable upregulation of immunoproteasomes. Next we addressed the question whether induction of HO-1 or its byproduct carbon monoxide (CO) in organ donors targets these candidate markers related to enhanced immunogenicity. Induction of HO-1 or CO in organ donors 24 h before organ harvesting resulted in reduced mRNA levels of immunoproteasomes, MHC class II expression, and co-stimulatory molecules in the recipient's spleen, suggesting diminished migration and activation of donor dendritic cells. This observation suggests that HO-1/CO induction protects marginal allografts by inhibiting the immunogenicity of donor-derived dendritic cells.