Neutrophil-related factors as biomarkers in EAE and MS.
Neutrophil-related factors as biomarkers in EAE and MS.
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DOI：
10.1084/jem.20141015
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发表时间：
2015-01-12
期刊：
影响因子：
--
通讯作者：
Segal BM
中科院分区：
文献类型：
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作者：
Rumble JM;Huber AK;Krishnamoorthy G;Srinivasan A;Giles DA;Zhang X;Wang L;Segal BM
作者使用多发性硬化症 (MS) 小鼠模型表明，中性粒细胞在临床发病前在骨髓中扩张并在循环中积聚。在疾病发展的早期，中性粒细胞浸润 CNS，G-CSF 受体缺陷和 CXCL1 阻断会抑制中性粒细胞浸润 CNS，从而改善疾病。在多发性硬化症患者中，中性粒细胞相关介质的全身表达与新病灶形成、病灶负担和临床残疾相关。辅助 T (Th) 17 细胞的主要功能是诱导产生激活和动员中性粒细胞的因子。尽管 Th17 细胞与多发性硬化症 (MS) 和动物模型实验性自身免疫性脑脊髓炎 (EAE) 的发病机制有关，但很少有人关注粒细胞在这些疾病中的作用。我们发现，在 EAE 临床发病前，中性粒细胞以及单核细胞在骨髓中扩增，并在循环中积聚，以响应粒细胞集落刺激因子 (G-CSF) 和 ELR+ CXC 趋化因子 CXCL1 的全身上调。在疾病发展早期，中性粒细胞在浸润中枢神经系统（CNS）的白细胞中所占比例相对较高。 G-CSF 受体缺陷和 CXCL1 阻断抑制了血液中骨髓细胞的积累，并改善了注射髓磷脂反应性 Th17 细胞的小鼠的临床病程。在复发性多发性硬化症患者中，另一种 ELR+ CXC 趋化因子 CXCL5 的血浆水平在急性病变形成过程中升高。 CXCL1、CXCL5 和中性粒细胞弹性蛋白酶的全身表达与 MS 病变负担和临床残疾的测量相关。基于这些结果，我们主张进一步研究中性粒细胞相关分子作为多发性硬化症的新型生物标志物和治疗靶点。
Using a mouse model of multiple sclerosis (MS), the authors show that neutrophils expand in the bone marrow and accumulate in the circulation before clinical onset of disease. Early in disease development, neutrophils infiltrate the CNS, which is suppressed by G-CSF receptor deficiency and blockade of CXCL1 to ameliorate disease. In patients with MS, systemic expression of neutrophil-related mediators correlates with new lesion formation, lesion burden, and clinical disability. A major function of T helper (Th) 17 cells is to induce the production of factors that activate and mobilize neutrophils. Although Th17 cells have been implicated in the pathogenesis of multiple sclerosis (MS) and the animal model experimental autoimmune encephalomyelitis (EAE), little attention has been focused on the role of granulocytes in those disorders. We show that neutrophils, as well as monocytes, expand in the bone marrow and accumulate in the circulation before the clinical onset of EAE, in response to systemic up-regulation of granulocyte colony-stimulating factor (G-CSF) and the ELR+ CXC chemokine CXCL1. Neutrophils comprised a relatively high percentage of leukocytes infiltrating the central nervous system (CNS) early in disease development. G-CSF receptor deficiency and CXCL1 blockade suppressed myeloid cell accumulation in the blood and ameliorated the clinical course of mice that were injected with myelin-reactive Th17 cells. In relapsing MS patients, plasma levels of CXCL5, another ELR+ CXC chemokine, were elevated during acute lesion formation. Systemic expression of CXCL1, CXCL5, and neutrophil elastase correlated with measures of MS lesion burden and clinical disability. Based on these results, we advocate that neutrophil-related molecules be further investigated as novel biomarkers and therapeutic targets in MS.
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影响因子：
3.7
作者：
Kadota R;Koda M;Kawabe J;Hashimoto M;Nishio Y;Mannoji C;Miyashita T;Furuya T;Okawa A;Takahashi K;Yamazaki M
通讯作者：
Yamazaki M
影响因子：
4.4
作者：
Ashton, EA;Takahashi, C;Ekholm, S
通讯作者：
Ekholm, S
影响因子：
3.3
作者：
Bell, MD;Taub, DD;Perry, VH
通讯作者：
Perry, VH
影响因子：
7
作者：
Becher B;Segal BM
通讯作者：
Segal BM
影响因子：
8
作者：
通讯作者：
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