McGonigle Terence A, Dwyer Amy R, Greenland Eloise L, Scott Naomi M, Keane Kevin N, Newsholme Philip, Goodridge Helen S, Zon Leonard I, Pixley Fiona J, Hart Prue H
Telethon Kids Institute, University of Western Australia, West Perth, Western Australia, Australia.
School of Biomedical Sciences, University of Western Australia, Western Australia, Australia.
Exp Hematol. 2017 Dec;56:64-68. doi: 10.1016/j.exphem.2017.08.002. Epub 2017 Aug 16.
Monocytes/macrophages differentiating from bone marrow (BM) cells pulsed for 2 hours at 37°C with a stabilized derivative of prostaglandin E, 16,16-dimethyl PGE (dmPGE), migrated less efficiently toward a chemoattractant than monocytes/macrophages differentiated from BM cells pulsed with vehicle. To confirm that the effect on BM cells was long lasting and to replicate human BM transplantation, chimeric mice were established with donor BM cells pulsed for 2 hours with dmPGE before injection into marrow-ablated congenic recipient mice. After 12 weeks, when high levels (90%) of engraftment were obtained, regenerated BM-derived monocytes/macrophages differentiating in vitro or in vivo migrated inefficiently toward the chemokines colony-stimulating factor-1 (CSF-1) and chemokine (C-C motif) ligand 2 (CCL2) or thioglycollate, respectively. Our results reveal long-lasting changes to progenitor cells of monocytes/macrophages by a 2-hour dmPGE pulse that, in turn, limits the migration of their daughter cells to chemoattractants and inflammatory mediators.
在37°C下用前列腺素E的稳定衍生物16,16 - 二甲基PGE（dmPGE）脉冲处理2小时的骨髓（BM）细胞分化而来的单核细胞/巨噬细胞，与用赋形剂脉冲处理的BM细胞分化而来的单核细胞/巨噬细胞相比，向趋化因子迁移的效率更低。为了证实对BM细胞的影响是持久的，并复制人类BM移植，在用dmPGE脉冲处理2小时后，将供体BM细胞注射到骨髓消融的同基因受体小鼠中，建立嵌合小鼠。12周后，当获得高水平（90%）的植入时，在体外或体内分化的再生BM来源的单核细胞/巨噬细胞分别向趋化因子集落刺激因子-1（CSF-1）、趋化因子（C-C基序）配体2（CCL2）或巯基乙酸盐迁移的效率低下。我们的结果揭示了通过2小时的dmPGE脉冲对单核细胞/巨噬细胞祖细胞产生的持久变化，这反过来又限制了它们的子代细胞向趋化因子和炎症介质的迁移。
