Yamaguchi Y, Suda T, Suda J, Eguchi M, Miura Y, Harada N, Tominaga A, Takatsu K
Department of Medicine, Jichi Medical School, Tochigi-Ken, Japan.
J Exp Med. 1988 Jan 1;167(1):43-56. doi: 10.1084/jem.167.1.43.
Using a clonal culture system, we investigated the hemopoietic effects of purified recombinant IL-5 obtained from conditioned media of transfected Xenopus oocytes. IL-5 alone acted on untreated bone marrow cells and supported the formation of a small number of colonies, all of which were predominantly eosinophilic. However, it did not support colony formation by spleen cells from 5-FU-treated mice, in which only primitive stem cells had survived, while IL-3 and G-CSF did. Eosinophil-containing colonies were formed from these cells in the presence of IL-5 and G-CSF together. In contrast, G-CSF alone did not support any eosinophil colonies. The eosinophilopoietic effect of IL-5 was dose-dependent, and was neutralized specifically by anti-IL-5 antibody. To exclude the possibility of interactions with accessory cells in the same culture dish, we replated a small number (200 cells/dish) of enriched hemopoietic progenitors, obtained from blast cell colonies, which were formed by cultivation of spleen cells from 5-FU-treated mice in the presence of IL-3 or G-CSF. From these replated blast cells, eosinophil colonies were induced in dishes containing IL-5 but not in those containing G-CSF alone. From these findings, it was concluded that IL-5 did not act on primitive hemopoietic cells, but on blast cells induced by IL-3 or G-CSF. IL-5 specifically facilitated the terminal differentiation and proliferation of eosinophils. In this respect, the role of IL-5 in eosinophilopoiesis seems to be analogous to erythropoietin, which promotes the terminal differentiation and amplification of erythroid cells. Moreover, IL-5 maintained the viability of mature eosinophils obtained from peritoneal exudate cells of the mice infected with parasites, indicating mature functional eosinophils carried IL-5 receptors. The synergistic effects of IL-5 and colony-stimulating factors on the expansion of eosinophils is supposed to contribute to the urgent mobilization of eosinophils at the time of helminthic infections and allergic responses.
利用克隆培养系统,我们研究了从转染非洲爪蟾卵母细胞的条件培养基中获得的纯化重组白细胞介素-5(IL-5)的造血作用。单独的IL-5作用于未处理的骨髓细胞,并支持形成少量集落,所有这些集落主要为嗜酸性粒细胞。然而,它不支持5-氟尿嘧啶(5-FU)处理小鼠的脾细胞形成集落,在这些小鼠中只有原始干细胞存活,而IL-3和粒细胞集落刺激因子(G-CSF)则可以。在IL-5和G-CSF共同存在的情况下,这些细胞形成了含嗜酸性粒细胞的集落。相比之下,单独的G-CSF不支持任何嗜酸性粒细胞集落。IL-5的嗜酸性粒细胞生成作用呈剂量依赖性,并被抗IL-5抗体特异性中和。为了排除与同一培养皿中辅助细胞相互作用的可能性,我们重新接种了少量(200个细胞/培养皿)从胚细胞集落中获得的富集造血祖细胞,这些胚细胞集落是通过在IL-3或G-CSF存在下培养5-FU处理小鼠的脾细胞形成的。从这些重新接种的胚细胞中,含IL-5的培养皿中诱导出嗜酸性粒细胞集落,而仅含G-CSF的培养皿中则未诱导出。从这些发现可以得出结论,IL-5不作用于原始造血细胞,而是作用于由IL-3或G-CSF诱导的胚细胞。IL-5特异性促进嗜酸性粒细胞的终末分化和增殖。在这方面,IL-5在嗜酸性粒细胞生成中的作用似乎类似于促红细胞生成素,后者促进红细胞的终末分化和扩增。此外,IL-5维持了从感染寄生虫小鼠的腹腔渗出细胞中获得的成熟嗜酸性粒细胞的活力,表明成熟的功能性嗜酸性粒细胞携带IL-5受体。IL-5与集落刺激因子对嗜酸性粒细胞扩增的协同作用被认为有助于在蠕虫感染和过敏反应时紧急动员嗜酸性粒细胞。