Differential expression of the human thymosin-beta 4 gene in lymphocytes, macrophages, and granulocytes.

Differential expression of the human thymosin-beta 4 gene in lymphocytes, macrophages, and granulocytes.
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DOI:
10.4049/jimmunol.139.11.3840
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发表时间:
1987-12
影响因子:
4.4
通讯作者:
H. Gondo;J. Kudo;J. W. White;C. Barr;P. Selvanayagam;G. Saunders
H. Gondo;J. Kudo;J. W. White;C. Barr;P. Selvanayagam;G. Saunders
中科院分区:
医学2区
文献类型:
--
作者:
H. Gondo;J. Kudo;J. W. White;C. Barr;P. Selvanayagam;G. Saunders

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从急性淋巴细胞白血病患者外周血白细胞制备的cDNA文库中分离出编码人胸腺素β 4的cDNA克隆。该克隆包含胸腺素β 4的43个氨基酸残基的完整编码序列,并具有一个起始密码子和两个终止密码子。编码区的氨基酸和核苷酸序列在大鼠和人之间具有很好的保守性。132个核苷酸中有9个核苷酸的编码序列不同(93%的同源性),但推导的氨基酸序列是相同的。在推导的蛋白质序列中未发现信号肽。人胸腺素β 4 mRNA长约830个核苷酸,比大鼠胸腺素β 4 mRNA长约30个核苷酸。研究了人胸腺素-β 4基因在各种原代骨髓和淋巴恶性细胞以及少数人造血细胞系中的表达。不同肿瘤性B淋巴细胞的北方印迹分析显示,胸腺素β 4 mRNA的稳态水平作为分化阶段的函数而变化。在骨髓瘤细胞中,胸腺素-β 4 mRNA水平降低,II类人类白细胞抗原、Fc受体和补体受体也降低,表明胸腺素-β 4与免疫应答之间存在关系。胸腺素β 4 mRNA在成熟粒细胞中的表达高于未成熟胚细胞。用重组人干扰素-λ处理THP-1细胞(一种人单核细胞系)可降低胸腺素-β 4 mRNA的水平。THP-1细胞分化为Ia+巨噬细胞后其水平降低,HL-60细胞分化为Ia-巨噬细胞后其水平升高。胸腺素β 4基因的表达模式表明,它可能在宿主防御机制中发挥重要作用。
A cDNA clone encoding human thymosin-beta 4 was isolated from a cDNA library prepared from peripheral blood leukocytes of a patient with acute lymphocytic leukemia. This clone contained the entire coding sequence of 43 amino acid residues of thymosin-beta 4 and had an initiation codon and two termination codons. The amino acid and nucleotide sequences in the coding region were well conserved between rat and human. Nine of 132 nucleotides were different in the coding sequences (93% homology), but the deduced amino acid sequences were identical. No signal peptide was found in the deduced protein sequence. Human thymosin-beta 4 mRNA, approximately 830 nucleotides in length, was about 30 nucleotides larger than rat thymosin-beta 4 mRNA. Expression of the human thymosin-beta 4 gene in various primary myeloid and lymphoid malignant cells and in a few human hemopoietic cell lines was studied. Northern blot analyses of different neoplastic B lymphocytes revealed that steady state levels of thymosin-beta 4 mRNA varied as a function of differentiation stage. Thymosin-beta 4 mRNA levels were decreased in myeloma cells as are class II human leukocyte antigen, Fc receptor, and complement receptor, suggesting a relationship between thymosin-beta 4 and the immune response. Thymosin-beta 4 mRNA was more highly expressed in mature granulocytes than in immature blastic cells. Treatment of THP-1 cells, a human monocytic cell line, with recombinant human interferon-lambda reduced the levels of thymosin-beta 4 mRNA. Its level decreased after differentiation of THP-1 cells into Ia+ macrophages, but increased after differentiation of HL-60 cells into Ia- macrophages. The pattern of thymosin-beta 4 gene expression suggests that it may play a fundamental role in the host defense mechanism.