Depletion of Macrophages and Dendritic Cells in Ischemic Acute Kidney Injury
Depletion of Macrophages and Dendritic Cells in Ischemic Acute Kidney Injury
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DOI：
10.1159/000335582
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发表时间：
2012-01-01
影响因子：
4.2
通讯作者：
Edelstein, Charles L.
中科院分区：
文献类型：
--
作者：
Lu, Lawrence;Faubel, Sarah;Edelstein, Charles L.
背景：炎症被认为在缺血性急性肾损伤（阿基）中起作用。我们已经证明，使用脂质体包封的氯膦酸二钠（LEC），巨噬细胞和树突状细胞的消耗，是对缺血性阿基的保护。研究方法：为了确定巨噬细胞或树突状细胞或两者是否在缺血性阿基中发挥作用，我们在白喉毒素（DT）诱导的CD 11b细胞（巨噬细胞）耗尽的CD 11b-DTR小鼠和DT诱导的CD 11 c细胞（树突状细胞）耗尽的CD 11 c-DTR小鼠中进行了缺血性阿基。结果如下：虽然LEC处理的动物对阿基具有显著的功能保护，但CD 11b-DTR和CD 11 c-DTR小鼠尽管肾巨噬细胞和树突状细胞消耗程度相似，但对阿基没有保护作用。已知促炎细胞因子在缺血性阿基中发挥作用。为了确定与经LEC处理的小鼠相比，CD 11b-DTR和CD 11 c-DTR小鼠缺乏保护的可能原因，在这些小鼠中测量了32种细胞因子/趋化因子。在所测量的细胞因子/趋化因子中，IL-6、MCP-1、GMCSF、IL-1 β和CXCL 1（在人类中也称为IL-8或在小鼠中称为KC）在LEE处理的、CD 11b-DTR和CD 11 c-DTR小鼠中显示出显著差异。MCP-1和CXCL 1（已知的阿基介质）以及GMCSF和IL-1 β在阿基中升高，在LEC治疗的阿基中降低，但在CD 11b-DTR或CD 11 c-DTR小鼠中不存在阿基。结论：这些发现表明，LEC介导的阿基保护作用并非简单地通过消耗肾巨噬细胞或树突状细胞亚群介导。与CD 11b-DTR或CD 11 c-DTR小鼠相比，LEC治疗小鼠对阿基的保护作用可能部分由促炎细胞因子谱的差异解释。版权所有（C）2012 S. Karger AG，巴塞尔
Background: Inflammation is thought to play a role in ischemic acute kidney injury (AKI). We have demonstrated that macrophage and dendritic cell depletion, using liposome-encapsulated clodronate (LEC), is protective against ischemic AKI. Methods: To determine whether macrophages or dendritic cells or both play a role in ischemic AKI, we performed ischemic AKI in CD11b-DTR mice that have a diphtheria toxin (DT)-induced depletion of CD11b cells (macrophages) and CD11c-DTR mice that have a DT-induced depletion of CD11c cells (dendritic cells). Results: While LEC-treated animals had a significant functional protection from AKI, CD11b-DTR and CD11c-DTR mice were not protected against AKI despite a similar degree of renal macrophage and dendritic cell depletion. Proinflammatory cytokines are known to play a role in ischemic AKI. To determine the possible reasons for the lack of protection in CD11b-DTR and CD11c-DTR mice compared to LEC-treated mice, 32 cytokines/chemokines were measured in these mice. Of the cytokines/chemokines measured, IL-6, MCP-1, GMCSF, IL-1 beta and CXCL1 (also known as IL-8 in humans or KC in mice) showed significant differences in the LEE-treated, CD11b-DTR and CD11c-DTR mice. MCP-1 and CXCL1 (known mediators of AKI), and also GMCSF and IL-1 beta were increased in AKI and decreased in LEC-treated AKI but not AKI in CD11b-DTR or CD11c-DTR mice. Conclusions: These findings suggest that LEC-mediated protection from AKI is not simply mediated by depletion of renal macrophage or dendritic cell subpopulations. Protection against AKI in LEC-treated compared to CD11b-DTR or CD11c-DTR mice may be partially explained by differences in proinflammatory cytokine profiles. Copyright (C) 2012 S. Karger AG, Basel