Zhan Chuan, Ma Cheng-bin, Yuan Hong-mou, Cao Bao-yuan, Zhu Jia-jun
Department of Orthopaedic Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang 110032, China.
Department of Orthopaedic Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang 110032, China.
Biochem Biophys Res Commun. 2015;468(1-2):343-8. doi: 10.1016/j.bbrc.2015.10.097. Epub 2015 Oct 22.
Macrophages have been implicated in peripheral nerve regeneration. However, whether macrophages-derived microvesicles (MVs) are involved in this process remains unknown. In the present study, the effects of macrophages-derived MVs on proliferation and migration of Schwann cells (SCs) were evaluated in both in vitro and in vivo.
Human monocytic leukaemia cell line (THP-1) was successfully driven to M1 and M2 phenotypes by delivery of either IFN-γ or IL-4, respectively. SCs incubated with M1 or M2 macrophages-derived MVs, the cell migration and proliferation were assessed, and expression levels of nerve growth factor (NGF) and Laminin were measured. A rat model of sciatic nerve was established and the effects of macrophages-derived MVs on nerve regeneration were investigated.
M2-derived MVs elevated migration, proliferation, NFG and Laminin protein levels of SCs compared with M1-or M0-derived MVs. The relative expression levels of miR-223 were also increased in M2 macrophages and M2-derived MVs. Transfected M2 macrophages with miR-223 inhibitor then co-incubated with SCs, an inhibition of cell migration and proliferation and a down-regulated levels of NFG and Laminin protein expression were observed. In vivo, M2-derived MVs significantly increased the infiltration and axon number of SCs.
M2-derived MVs promoted proliferation and migration of SCs in vitro and in vivo, which provided a therapeutic strategy for nerve regeneration.
巨噬细胞与周围神经再生有关。然而，巨噬细胞衍生的微泡（MVs）是否参与这一过程仍不清楚。在本研究中，在体外和体内评估了巨噬细胞衍生的MVs对雪旺细胞（SCs）增殖和迁移的影响。
通过分别递送IFN-γ或IL-4，成功将人单核细胞白血病细胞系（THP-1）诱导为M1和M2表型。将SCs与M1或M2巨噬细胞衍生的MVs共同孵育，评估细胞迁移和增殖情况，并测量神经生长因子（NGF）和层粘连蛋白的表达水平。建立大鼠坐骨神经模型，研究巨噬细胞衍生的MVs对神经再生的影响。
与M1或M0衍生的MVs相比，M2衍生的MVs提高了SCs的迁移、增殖、NFG和层粘连蛋白蛋白水平。M2巨噬细胞和M2衍生的MVs中miR-223的相对表达水平也有所增加。用miR-223抑制剂转染M2巨噬细胞，然后与SCs共同孵育，观察到细胞迁移和增殖受到抑制，NFG和层粘连蛋白蛋白表达水平下调。在体内，M2衍生的MVs显著增加了SCs的浸润和轴突数量。
M2衍生的MVs在体外和体内均促进了SCs的增殖和迁移，为神经再生提供了一种治疗策略。
