Scavenger receptor collectin placenta 1 is a novel receptor involved in the uptake of myelin by phagocytes
Scavenger receptor collectin placenta 1 is a novel receptor involved in the uptake of myelin by phagocytes
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DOI：
10.1038/srep44794
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发表时间：
2017-03-20
影响因子：
4.6
通讯作者：
Hendriks, Jerome J. A.
中科院分区：
文献类型：
--
作者：
Bogie, Jeroen F. J.;Mailleux, Jo;Hendriks, Jerome J. A.
含髓磷脂的巨噬细胞和小胶质细胞是活动性多发性硬化症 (MS) 病变中最丰富的免疫细胞。我们最近的转录组分析表明，胎盘集合素 1 (CL-P1) 是巨噬细胞摄取髓磷脂后最有效的诱导基因之一。 CL-P1 是一种 II 型跨膜蛋白，具有类胶原蛋白和碳水化合物识别结构域，在宿主防御中发挥关键作用。在本研究中，我们试图确定含髓磷脂吞噬细胞上 CL-P1 表达的动态，并确定其在 MS 病变发展中所起的作用。我们发现，在体外，髓磷脂的摄取会增加小鼠和人类巨噬细胞的细胞表面 CL-P1 表达，但不会增加原代小鼠小胶质细胞的细胞表面表达。在活动性脱髓鞘性多发性硬化症病变中，CL-P1 免疫反应性局限于血管周围和实质内充满髓磷脂的吞噬细胞。最后，我们证明 CL-P1 参与髓磷脂内化，因为 CL-P1 的敲除显着减少了髓磷脂的摄取。总的来说，我们的数据表明 CL-P1 是一种参与吞噬细胞髓磷脂摄取的新型受体，并且可能在 MS 病变发展中发挥作用。
Myelin-containing macrophages and microglia are the most abundant immune cells in active multiple sclerosis (MS) lesions. Our recent transcriptomic analysis demonstrated that collectin placenta 1 (CL-P1) is one of the most potently induced genes in macrophages after uptake of myelin. CL-P1 is a type II transmembrane protein with both a collagen-like and carbohydrate recognition domain, which plays a key role in host defense. In this study we sought to determine the dynamics of CL-P1 expression on myelin-containing phagocytes and define the role that it plays in MS lesion development. We show that myelin uptake increases the cell surface expression of CL-P1 by mouse and human macrophages, but not by primary mouse microglia in vitro. In active demyelinating MS lesions, CL-P1 immunoreactivity was localized to perivascular and parenchymal myelin-laden phagocytes. Finally, we demonstrate that CL-P1 is involved in myelin internalization as knockdown of CL-P1 markedly reduced myelin uptake. Collectively, our data indicate that CL-P1 is a novel receptor involved in myelin uptake by phagocytes and likely plays a role in MS lesion development.