McGonigle Terence A, Dwyer Amy R, Greenland Eloise L, Scott Naomi M, Carter Kim W, Keane Kevin N, Newsholme Philip, Goodridge Helen S, Pixley Fiona J, Hart Prue H
Telethon Kids Institute, University of Western Australia, West Perth, Western Australia 6872, Australia.
School of Biomedical Sciences, University of Western Australia, Western Australia 6009, Australia.
J Immunol. 2018 Jan 1;200(1):260-270. doi: 10.4049/jimmunol.1700760. Epub 2017 Nov 22.
The ability of macrophages to respond to chemoattractants and inflammatory signals is important for their migration to sites of inflammation and immune activity and for host responses to infection. Macrophages differentiated from the bone marrow (BM) of UV-irradiated mice, even after activation with LPS, migrated inefficiently toward CSF-1 and CCL2. When BM cells were harvested from UV-irradiated mice and transplanted into naive mice, the recipient mice (UV-chimeric) had reduced accumulation of elicited monocytes/macrophages in the peritoneal cavity in response to inflammatory thioglycollate or alum. Macrophages differentiating from the BM of UV-chimeric mice also had an inherent reduced ability to migrate toward chemoattractants in vitro, even after LPS activation. Microarray analysis identified reduced reticulon-1 mRNA expressed in macrophages differentiated from the BM of UV-chimeric mice. By using an anti-reticulon-1 Ab, a role for reticulon-1 in macrophage migration toward both CSF-1 and CCL2 was confirmed. Reticulon-1 subcellular localization to the periphery after exposure to CSF-1 for 2.5 min was shown by immunofluorescence microscopy. The proposal that reduced reticulon-1 is responsible for the poor inherent ability of macrophages to respond to chemokine gradients was supported by Western blotting. In summary, skin exposure to erythemal UV radiation can modulate macrophage progenitors in the BM such that their differentiated progeny respond inefficiently to signals to accumulate at sites of inflammation and immunity.
巨噬细胞对趋化因子和炎症信号作出反应的能力，对于其向炎症和免疫活动部位迁移以及宿主对感染的反应而言至关重要。即使在用脂多糖（LPS）激活后，源自紫外线照射小鼠骨髓（BM）的巨噬细胞向集落刺激因子-1（CSF-1）和CC趋化因子配体2（CCL2）的迁移效率依然低下。当从紫外线照射小鼠采集骨髓细胞并移植到未接触过病原体的小鼠体内时，受体小鼠（紫外线嵌合体）对炎症性巯基乙酸盐或明矾的反应中，腹腔内募集的单核细胞/巨噬细胞数量减少。即使在LPS激活后，源自紫外线嵌合体小鼠骨髓的巨噬细胞在体外向趋化因子迁移的内在能力也同样降低。微阵列分析发现，源自紫外线嵌合体小鼠骨髓的巨噬细胞中，网质蛋白-1（reticulon-1）mRNA的表达量减少。通过使用抗网质蛋白-1抗体，证实了网质蛋白-1在巨噬细胞向CSF-1和CCL2迁移过程中的作用。免疫荧光显微镜显示，在接触CSF-1 2.5分钟后，网质蛋白-1在亚细胞水平定位于细胞周边。蛋白质印迹法支持了网质蛋白-1减少导致巨噬细胞对趋化因子梯度反应的内在能力较差这一观点。总之，皮肤暴露于红斑性紫外线辐射可调节骨髓中的巨噬细胞祖细胞，使其分化后代对炎症和免疫部位的聚集信号反应不佳。
