Takizawa Naoki, Okubo Naoto, Kamo Masaharu, Chosa Naoyuki, Mikami Toshinari, Suzuki Keita, Yokota Seiji, Ibi Miho, Ohtsuka Masato, Taira Masayuki, Yaegashi Takashi, Ishisaki Akira, Kyakumoto Seiko
Division of Cellular Biosignal Sciences, Department of Biochemistry, Iwate Medical University, 2-1-1 Nishitokuta, Yahaba-cho, Shiwa-gun, Iwate 028-3694, Japan; Division of Periodontology, Department of Conservative Dentistry, School of Dentistry, Iwate Medical University, 1-3-27 Chuo-dori, Morioka-shi, Iwate 020-8505, Japan.
Division of Cellular Biosignal Sciences, Department of Biochemistry, Iwate Medical University, 2-1-1 Nishitokuta, Yahaba-cho, Shiwa-gun, Iwate 028-3694, Japan; Laboratory of Pathophysiology and Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-ku, Sapporo, Hokkaido 060-0812, Japan.
Exp Cell Res. 2017 Sep 15;358(2):411-420. doi: 10.1016/j.yexcr.2017.07.014. Epub 2017 Jul 14.
Immunosuppressive/anti-inflammatory macrophage (Mφ), M2-Mφ that expressed the typical M2-Mφs marker, CD206, and anti-inflammatory cytokine, interleukin (IL)-10, is beneficial and expected tool for the cytotherapy against inflammatory diseases. Here, we demonstrated that bone marrow-derived lineage-positive (Lin+) blood cells proliferated and differentiated into M2-Mφs by cooperation with the bone marrow-derived mesenchymal stem cells (MSCs) under hypoxic condition: MSCs not only promoted proliferation of undifferentiated M2-Mφs, pre-M2-Mφs, in the Lin+ fraction via a proliferative effect of the MSCs-secreted macrophage colony-stimulating factor, but also promoted M2-Mφ polarization of the pre-M2-Mφs through cell-to-cell contact with the pre-M2-Mφs. Intriguingly, an inhibitor for intercellular adhesion molecule (ICAM)-1 receptor/lymphocyte function-associated antigen (LFA)-1, Rwj50271, partially suppressed expression of CD206 in the Lin+ blood cells but an inhibitor for VCAM-1 receptor/VLA-4, BIO5192, did not, suggesting that the cell-to-cell adhesion through LFA-1 on pre-M2-Mφs and ICAM-1 on MSCs was supposed to promoted the M2-Mφ polarization. Thus, the co-culture system consisting of bone marrow-derived Lin+ blood cells and MSCs under hypoxic condition was a beneficial supplier of a number of M2-Mφs, which could be clinically applicable to inflammatory diseases.
免疫抑制/抗炎性巨噬细胞（Mφ），即表达典型M2-Mφ标志物CD206和抗炎细胞因子白细胞介素（IL）-10的M2-Mφ，是用于炎症性疾病细胞治疗的有益且值得期待的工具。在此，我们证明了骨髓来源的谱系阳性（Lin+）血细胞在低氧条件下与骨髓来源的间充质干细胞（MSC）协同作用，能够增殖并分化为M2-Mφ：MSC不仅通过其分泌的巨噬细胞集落刺激因子的增殖作用促进Lin+组分中未分化的M2-Mφ（前M2-Mφ）的增殖，还通过与前M2-Mφ的细胞间接触促进前M2-Mφ向M2-Mφ的极化。有趣的是，细胞间黏附分子（ICAM）-1受体/淋巴细胞功能相关抗原（LFA）-1的抑制剂Rwj50271可部分抑制Lin+血细胞中CD206的表达，但血管细胞黏附分子（VCAM）-1受体/VLA-4的抑制剂BIO5192则无此作用，这表明前M2-Mφ上的LFA-1与MSC上的ICAM-1之间的细胞间黏附可能促进了M2-Mφ的极化。因此，低氧条件下由骨髓来源的Lin+血细胞和MSC组成的共培养系统是大量M2-Mφ的有益来源，可在临床上应用于炎症性疾病。
