Ohnmacht Caspar, Pullner Andrea, van Rooijen Nico, Voehringer David
Institute for Immunology, University of Munich, Munich, Germany.
J Immunol. 2007 Oct 1;179(7):4766-74. doi: 10.4049/jimmunol.179.7.4766.
Eosinophils are potent effector cells associated with allergic inflammation and parasite infections. However, limited information exists about their turnover, migration, and survival in vivo. To address these important questions, we determined murine eosinophil turnover under steady state and inflammatory conditions by flow cytometric analysis of BrdU incorporation and analyzed their migration pattern and survival in different tissues after adoptive transfer into recipient mice. In naive mice approximately 50% of bone marrow eosinophils were labeled with BrdU during a 15-h pulse, whereas only 10% of splenic eosinophils were labeled within this time frame. Unexpectedly, the rate of eosinophil production did not change during acute infection with the helminth parasite Nippostrongylus brasiliensis despite massive eosinophilia in several tissues. Eosinophils present in lung and peritoneum remained largely BrdU negative, indicating that eosinophilia in end organs was mainly caused by increased survival of already existing eosinophils rather than increased production of new eosinophils in the bone marrow. Adoptive transfer experiments revealed that eosinophils preferentially migrated to the peritoneum in a macrophage-independent and pertussis toxin-sensitive manner, where they survived for several days. Peritoneal eosinophils expressed high levels of the inhibitory receptor Siglec-F, released less eosinophil peroxidase compared with eosinophils from the spleen, and could recirculate to other organs. These results demonstrate that the peritoneum serves as reservoir for eosinophils.
嗜酸性粒细胞是与过敏性炎症和寄生虫感染相关的强效效应细胞。然而,关于它们在体内的更新、迁移和存活的信息有限。为了解决这些重要问题,我们通过对BrdU掺入的流式细胞术分析确定了稳态和炎症条件下小鼠嗜酸性粒细胞的更新,并分析了它们在过继转移到受体小鼠后在不同组织中的迁移模式和存活情况。在未感染的小鼠中,在15小时的脉冲期间,约50%的骨髓嗜酸性粒细胞被BrdU标记,而在此时间范围内脾脏嗜酸性粒细胞仅有10%被标记。出乎意料的是,尽管在几个组织中出现大量嗜酸性粒细胞增多,但在感染巴西日圆线虫这种蠕虫寄生虫的急性感染期间,嗜酸性粒细胞的产生速率并未改变。肺和腹膜中的嗜酸性粒细胞大多仍为BrdU阴性,这表明终末器官中的嗜酸性粒细胞增多主要是由于已有嗜酸性粒细胞的存活增加,而非骨髓中新生嗜酸性粒细胞的产生增加。过继转移实验表明,嗜酸性粒细胞以巨噬细胞非依赖且对百日咳毒素敏感的方式优先迁移至腹膜,在那里它们可存活数天。腹膜嗜酸性粒细胞表达高水平的抑制性受体Siglec-F,与脾脏嗜酸性粒细胞相比释放较少的嗜酸性粒细胞过氧化物酶,并且可以再循环至其他器官。这些结果表明腹膜是嗜酸性粒细胞的储存库。