Macrophage Polarization Modulates Development of Systemic Lupus Erythematosus
Macrophage Polarization Modulates Development of Systemic Lupus Erythematosus
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DOI：
10.1159/000430251
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发表时间：
2015-01-01
影响因子：
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通讯作者：
Xu, Jinhua
中科院分区：
文献类型：
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作者：
Li, Feng;Yang, Yongsheng;Xu, Jinhua
背景/目的：巨噬细胞最近被证明在系统性红斑狼疮（SLE）的发病机制中发挥着关键作用。然而，其根本机制仍不清楚。方法：在这里，我们使用活化淋巴细胞源性 DNA (ALD-DNA) 方法诱导小鼠 SLE。我们使用巨噬细胞特异性消除剂氯膦酸盐选择性地消除小鼠中的巨噬细胞。我们从小鼠骨髓中分离出巨噬细胞，并使用细胞因子分别区分M1和M2巨噬细胞。在氯膦酸盐治疗的小鼠中进行 M1 或 M2 巨噬细胞的过继移植。通过血清抗 dsDNA 自身抗体、肾脏病理变化和尿蛋白水平评估对 SLE 的影响。结果：ALD-DNA 诱导小鼠出现 SLE 样特征，表现为血清抗 dsDNA 自身抗体的诱导、肾脏病理变化以及尿蛋白水平增加。氯膦酸盐显着减少小鼠巨噬细胞，从而显着增加系统性红斑狼疮的严重程度。在氯膦酸盐和 ALD-DNA 治疗的小鼠中，M2 巨噬细胞而非 M1 巨噬细胞的过继移植显着降低了 SLE 的严重程度。结论：M1和M2巨噬细胞在SLE的发生发展中发挥不同的作用。 M1 巨噬细胞会加重 SLE 的严重程度，而 M2 巨噬细胞会减轻 SLE 的严重程度。调节巨噬细胞极性可能是治疗 SLE 的一种有吸引力的疗法。版权所有 (C) 2015 S. Karger AG，巴塞尔
Background/Aims: Macrophages have recently been shown to play a critical role in the pathogenesis of systemic lupus erythematosus (SLE). However, the underlying mechanisms remain unclear. Methods: Here, we used an activated lymphocyte-derived DNA (ALD-DNA) method to induce SLE in mice. We used a macrophage-specific eliminator clodronate to selectively deplete macrophages in mice. We isolated macrophages from bone marrow of the mice and used cytokines to differentiate M1 and M2 macrophages, respectively. Adoptive transplantation of M1 or M2 macrophages was performed in clodronate-treated mice. The effects on SLE were evaluated by serum anti-dsDNA autoantibody, by renal pathological changes, and by urine protein levels. Results: ALD-DNA induced SLE-like features in mice, manifested by induction of serum anti-dsDNA autoantibody, by renal pathological changes, and by increases in urine protein levels. Clodronate significantly decreased macrophages in mice, which significantly increased SLE severity. Adoptive transplantation of M2, but not M1 macrophages significantly reduced SLE severity in clodronate- and ALD-DNA-treated mice. Conclusion: M1 and M2 macrophages play different roles in development of SLE. M1 macrophages increase the severity of SLE, while M2 macrophages reduce it. Modulation of macrophage polarity may be an attractive therapy for SLE. Copyright (C) 2015 S. Karger AG, Basel