Strath M, Dent L, Sanderson C
National Institute for Medical Research, Mill Hill, London, England.
Exp Hematol. 1992 Feb;20(2):229-34.
Transgenic mice expressing interleukin 5 (IL5) have been demonstrated to show a lifelong high level eosinophilia. These mice were produced using a construct in which the dominant control region (DCR) of the human CD2 gene was ligated to a 10-kb fragment containing the mouse IL5 gene. The construct allows the expression of the IL5 gene under the control of its own promoter, but the DCR ensures constitutive expression by all T cells. Infection of these transgenic mice with Mesocestoides corti, which is itself a potent inducer of eosinophilia, increases serum IL5 to very high levels. This demonstrates that the transgenes retain inducibility, which is a feature of the endogenous gene. However, despite the high levels of IL5, the numbers of eosinophils in the blood, marrow, and spleen decrease during the period 1-4 weeks after infection. Furthermore, there is a decrease in eosinophil precursors, as assessed by the capacity of bone marrow to produce eosinophils in culture. After this decrease eosinophils return to their previous high levels, although the levels of IL5 remain high. These results suggest that a control mechanism is operating to limit the numbers of eosinophils produced. This control appears to act at the level of the precursor production and may not be directly related to the high levels of IL5.
已证明表达白细胞介素5(IL5)的转基因小鼠表现出终身高水平的嗜酸性粒细胞增多。这些小鼠是通过一种构建体产生的,其中人CD2基因的显性控制区(DCR)与包含小鼠IL5基因的10 kb片段连接。该构建体允许IL5基因在其自身启动子的控制下表达,但DCR确保所有T细胞的组成型表达。用本身就是嗜酸性粒细胞增多的强效诱导剂的柯氏中殖孔绦虫感染这些转基因小鼠,会使血清IL5升高到非常高的水平。这表明转基因保留了可诱导性,这是内源基因的一个特征。然而,尽管IL5水平很高,但在感染后1 - 4周期间,血液、骨髓和脾脏中的嗜酸性粒细胞数量减少。此外,通过骨髓在培养中产生嗜酸性粒细胞的能力评估,嗜酸性粒细胞前体数量减少。在这种减少之后,嗜酸性粒细胞恢复到之前的高水平,尽管IL5水平仍然很高。这些结果表明存在一种控制机制在限制产生的嗜酸性粒细胞数量。这种控制似乎作用于前体产生水平,可能与高水平的IL5没有直接关系。