Mobilisation of the splenic monocyte reservoir and peripheral CX3CR1 deficiency adversely affects recovery from spinal cord injury
Mobilisation of the splenic monocyte reservoir and peripheral CX3CR1 deficiency adversely affects recovery from spinal cord injury
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DOI：
10.1016/j.expneurol.2013.05.002
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发表时间：
2013-09-01
影响因子：
5.3
通讯作者：
Ruitenberg, Marc J.
中科院分区：
文献类型：
--
作者：
Blomster, Linda V.;Brennan, Faith H.;Ruitenberg, Marc J.
受损脊髓中的巨噬细胞源自驻留的小胶质细胞和血液单核细胞。这种起源的多样性是否导致它们在免疫病理学和修复过程中看似双重的作用仍然知之甚少。在这里，我们利用 Cx(3)cr1(gfp) 小鼠，通过过继细胞转移和骨髓 (BM) 嵌合体方法观察受损脊髓中单核细胞衍生的巨噬细胞。我们发现，损伤后 7 天时，大多数浸润单核细胞源自脾脏，只有较小程度源自骨髓。通过脾切除术预防早期单核细胞浸润与 SCI 后 42 天恢复的改善有关。此外，由于外周免疫区室中CX(3)CR1缺陷，早期存在的浸润单核细胞/巨噬细胞增加，与损伤结果恶化相关。已识别的 Cx(3)cr1(gfp/+) 单核细胞的过继转移证实了损伤后 7 天的浸润高峰，其中炎症（Ly6C（高））单核细胞最有效地募集：局灶性 SCI 还改变了血液中两个主要单核细胞亚群的组成，在高峰募集期间存在更多的 Ly6C（高）细胞。过继转移实验进一步表明损伤后 7 天脊髓中炎症单核细胞的高周转率。与此一致的是，此时只有一小部分浸润细胞明确表达促炎（M1）或替代激活（M2）巨噬细胞的极化标记。我们的研究结果为 SCI 后单核细胞衍生巨噬细胞的起源及其对功能恢复的贡献提供了新的见解，为进一步审查和选择性靶向 Ly6C（高）单核细胞以改善神经创伤事件的结果提供了基础。 (C) 2013 Elsevier Inc. 保留所有权利。
Macrophages in the injured spinal cord originate from resident microglia and blood monocytes. Whether this diversity in origins contributes to their seemingly dual role in immunopathology and repair processes has remained poorly understood. Here we took advantage of Cx(3)cr1(gfp) mice to visualise monocyte-derived macrophages in the injured spinal cord via adoptive cell transfer and bone marrow (BM) chimera approaches. We show that the majority of infiltrating monocytes at 7 days post-injury originate from the spleen and only to a lesser extent from the BM. Prevention of early monocyte infiltration via splenectomy was associated with improved recovery at 42 days post-SCI. In addition, an increased early presence of infiltrating monocytes/macrophages, as a result of CX(3)CR1 deficiency within the peripheral immune compartment, correlated with worsened injury outcomes. Adoptive transfer of identified Cx(3)cr1(gfp/+) monocytes confirmed peak infiltration at 7 days post-injury, with inflammatory (Ly6C(high)) monocytes being most efficiently recruited: Focal SCI also changed the composition of the two major monocyte subsets in the blood, with more Ly6C(high) cells present during peak recruitment. Adoptive transfer experiments further suggested high turnover of inflammatory monocytes in the spinal cord at 7 days post-injury. Consistent with this, only a small proportion of infiltrating cells unequivocally expressed polarisation markers for pro-inflammatory (M1) or alternatively activated (M2) macrophages at this time point. Our findings offer new insights into the origins of monocyte-derived macrophages after SCI and their contribution to functional recovery, providing a basis for further scrutiny and selective targeting of Ly6C(high) monocytes to improve outcomes from neurotraumatic events. (C) 2013 Elsevier Inc. All rights reserved.