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人类嗜酸性粒细胞分化因子(白细胞介素5)编码基因的分子克隆、核苷酸序列及表达

Molecular cloning, nucleotide sequence, and expression of the gene encoding human eosinophil differentiation factor (interleukin 5).

作者信息

Campbell H D, Tucker W Q, Hort Y, Martinson M E, Mayo G, Clutterbuck E J, Sanderson C J, Young I G

机构信息

Medical Molecular Biology Unit, John Curtin School of Medical Research, Australian National University, Canberra, A.C.T.

出版信息

Proc Natl Acad Sci U S A. 1987 Oct;84(19):6629-33. doi: 10.1073/pnas.84.19.6629.

Abstract

The human eosinophil differentiation factor (EDF) gene was cloned from a genomic library in lambda phage EMBL3A by using a murine EDF cDNA clone as a probe. The DNA sequence of a 3.2-kilobase BamHI fragment spanning the gene was determined. The gene contains three introns. The predicted amino acid sequence of 134 amino acids is identical with that recently reported for human interleukin 5 but shows no significant homology with other known hemopoietic growth regulators. The amino acid sequence shows strong homology (approximately 70% identity) with that of murine EDF. Recombinant human EDF, expressed from the human EDF gene after transfection into monkey COS cells, stimulated the production of eosinophils and eosinophil colonies from normal human bone marrow but had no effect on the production of neutrophils or mononuclear cells (monocytes and lymphoid cells). The apparent specificity of human EDF for the eosinophil lineage in myeloid hemopoiesis contrasts with the properties of human interleukin 3 and granulocyte/macrophage and granulocyte colony-stimulating factors but is directly analogous to the biological properties of murine EDF. Human EDF therefore represents a distinct hemopoietic growth factor that could play a central role in the regulation of eosinophilia.

摘要

通过使用鼠嗜酸性粒细胞分化因子(EDF)cDNA克隆作为探针,从λ噬菌体EMBL3A基因组文库中克隆了人类嗜酸性粒细胞分化因子(EDF)基因。测定了跨越该基因的一个3.2千碱基BamHI片段的DNA序列。该基因含有三个内含子。预测的134个氨基酸的氨基酸序列与最近报道的人类白细胞介素5相同,但与其他已知的造血生长调节因子没有明显的同源性。该氨基酸序列与鼠EDF的氨基酸序列具有很强的同源性(约70%的同一性)。将人类EDF基因转染到猴COS细胞后表达的重组人EDF刺激了正常人骨髓中嗜酸性粒细胞和嗜酸性粒细胞集落的产生,但对中性粒细胞或单核细胞(单核细胞和淋巴细胞)的产生没有影响。人EDF在髓系造血中对嗜酸性粒细胞谱系的明显特异性与人类白细胞介素3、粒细胞/巨噬细胞和粒细胞集落刺激因子的特性形成对比,但与鼠EDF的生物学特性直接类似。因此,人EDF代表一种独特的造血生长因子,可能在嗜酸性粒细胞增多症的调节中起核心作用。

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