Eosinophilia in transgenic mice expressing interleukin 5.
Eosinophilia in transgenic mice expressing interleukin 5.
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DOI：
10.1084/jem.172.5.1425
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发表时间：
1990-11-01
期刊：
影响因子：
--
通讯作者：
Sanderson CJ
中科院分区：
文献类型：
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作者：
Dent LA;Strath M;Mellor AL;Sanderson CJ
体外实验表明，尽管白细胞介素5 （IL-5）刺激嗜酸性粒细胞分化的后期，但嗜酸性粒细胞祖细胞的产生需要其他细胞因子。在这项研究中，利用IL-5基因的基因组片段与编码人类CD2基因的显性控制区偶联，建立了组成性表达IL-5基因的转基因小鼠。迄今为止，已经建立了四个独立的嗜酸性转基因系，其中两个有8个和49个转基因拷贝，并进行了详细描述。这些小鼠除脾肿大外，在宏观上表现正常。与正常窝鼠相比，转基因鼠血液中的嗜酸性粒细胞至少高出65至265倍，而与感染了蠕虫corti的小鼠相比，转基因鼠血液中的嗜酸性粒细胞大约高出2至7倍。与正常窝鼠相比，转基因鼠的血液中性粒细胞、淋巴细胞和单核细胞数量的增加要温和得多（不到三倍）。因此，IL-5在体内对嗜酸性粒细胞谱系具有相对特异性。脾脏、骨髓和腹膜渗出液中均有大量嗜酸性粒细胞，且在转基因拷贝数最多的细胞系中嗜酸性粒细胞最多。在转基因肺、Peyer’s斑块、肠系膜淋巴结和肠固有层的组织学切片中也发现嗜酸性粒细胞增多，但在其他组织中未见。在转基因动物血清中检测到的IL-5水平与寄生虫感染动物血清中检测到的水平相当。未发现IL-3和粒细胞/巨噬细胞集落刺激因子（GM-CSF）。IL-5 mRNA在转基因胸腺、Peyer’s斑块和浅表淋巴结中检测到，但在心脏、肝脏、大脑、骨骼肌或任何非转基因组织中未检测到。转基因小鼠骨髓中富含il -5依赖性嗜酸性粒细胞前体。这些数据表明，诱导IL-5基因足以产生嗜酸性粒细胞，并且IL-5可以诱导嗜酸性粒细胞分化的完整途径。因此，IL-5的作用可能不局限于嗜酸性粒细胞分化的后期，正如早期的体外研究所表明的那样。
Experiments in vitro suggest that although interleukin 5 (IL-5) stimulates the late stages of eosinophil differentiation, other cytokines are required for the generation of eosinophil progenitor cells. In this study transgenic mice constitutively expressing the IL-5 gene were established using a genomic fragment of the IL-5 gene coupled to the dominant control region from the gene encoding human CD2. Four independent eosinophilic transgenic lines have thus far been established, two of which with 8 and 49 transgene copies, are described in detail. These mice appeared macroscopically normal apart from splenomegaly. Eosinophils were at least 65- and 265-fold higher in blood from transgenics, relative to normal littermates, and approximately two- or sevenfold more numerous relative to blood from mice infected with the helminth Mesocestoides corti. Much more modest increases in blood neutrophil, lymphocyte, and monocyte numbers were noted in transgenics, relative to normal littermates (less than threefold). Thus IL-5 in vivo is relatively specific for the eosinophil lineage. Large numbers of eosinophils were present in spleen, bone marrow, and peritoneal exudate, and were highest in the line with the greatest transgene copy number. Eosinophilia was also noted in histological sections of transgenic lungs, Peyer's patches, mesenteric lymph nodes, and gut lamina propria but not in other tissues examined. IL-5 was detected in the sera of transgenics at levels comparable to those seen in sera from parasite-infected animals. IL-3 and granulocyte/macrophage colony-stimulating factor (GM-CSF) were not found. IL-5 mRNA was detected in transgenic thymus, Peyer's patches, and superficial lymph nodes, but not in heart, liver, brain, or skeletal muscle or in any tissues from nontransgenics. Bone marrow from transgenic mice was rich in IL-5-dependent eosinophil precursors. These data indicate that induction of the IL-5 gene is sufficient for production of eosinophilia, and that IL-5 can induce the full pathway of eosinophil differentiation. IL-5 may therefore not be restricted in action to the later stages of eosinophil differentiation, as suggested by earlier in vitro studies.