Fux Michaela, van Rooijen Nico, Owens Trevor
Medical Biotechnology Center, University of Southern Denmark, Winsloewparken 25, DK-5000 Odense C, Denmark.
J Neuroimmunol. 2008 Oct 15;203(1):64-72. doi: 10.1016/j.jneuroim.2008.06.025.
We have addressed the role of macrophages in glial response and T cell entry to the CNS after axonal injury, by using intravenous injection of clodronate-loaded mannosylated liposomes, in C57BL6 mice. As expected, clodronate-liposome treatment resulted in depletion of peripheral macrophages which was confirmed by F4/80- and MOMA-1(-) stainings in spleen. Sequential clodronate-liposome treatment 4, 2 and 0 days before axotomy resulted in significant reduction of infiltrating CD45(high) CD11b+ macrophages in the hippocampus at 1, 2 and 3 days post-lesion, measured by flow cytometry. There was a slight delay in the expansion of CD45(dim) CD11+ microglia in clodronate-liposome treated mice, but macrophage depletion had no effect on the percentage of infiltrating T cells in the lesion-reactive hippocampus. Lesion-induced TNFalpha mRNA expression was not affected by macrophage depletion, suggesting that activated glial cells are the primary source of this cytokine in the axonal injury-reactive brain. This identifies a potentially important distinction from inflammatory autoimmune infiltration in EAE, where macrophages are a prominent source of TNFalpha and their depletion prevents parenchymal T cell infiltration and disease.
我们通过给C57BL6小鼠静脉注射负载氯膦酸盐的甘露糖基化脂质体，研究了巨噬细胞在轴突损伤后神经胶质反应和T细胞进入中枢神经系统过程中的作用。正如预期的那样，氯膦酸盐脂质体处理导致外周巨噬细胞耗竭，这通过脾脏中F4/80和MOMA-1（-）染色得以证实。在轴突切断术前4天、2天和0天进行连续氯膦酸盐脂质体处理，通过流式细胞术检测发现，损伤后1天、2天和3天海马中浸润的CD45（高）CD11b +巨噬细胞显著减少。在氯膦酸盐脂质体处理的小鼠中，CD45（低）CD11 +小胶质细胞的扩增略有延迟，但巨噬细胞耗竭对损伤反应性海马中浸润T细胞的百分比没有影响。损伤诱导的TNFα mRNA表达不受巨噬细胞耗竭的影响，这表明活化的神经胶质细胞是轴突损伤反应性大脑中这种细胞因子的主要来源。这确定了与实验性自身免疫性脑脊髓炎（EAE）中炎症性自身免疫浸润的一个潜在重要区别，在EAE中，巨噬细胞是TNFα的主要来源，它们的耗竭可防止实质T细胞浸润和疾病发生。
