Iizasa T, Kubota M, Carson D A
J Immunol. 1983 Oct;131(4):1776-9.
The association of a genetic deficiency of adenosine deaminase (ADA) with immunodeficiency disease has emphasized the importance of deoxyadenosine and adenosine metabolism for human lymphocyte function. However, information concerning the endogenous production and metabolism of deoxyadenosine and adenosine in normally growing human T and B lymphoblasts is lacking. In the present experiments, we used a diverse series of cell lines deficient in individual enzymes of purine metabolism to quantitate the de novo formation of deoxyadenosine and adenosine in human T lymphoblasts (CEM), B lymphoblasts (WI-L2), and histiocytic lymphoma cells (DHL-9). The B lymphoblasts and histiocytic lymphoma cells generated deoxyadenosine at a rate of 60 to 80 pmol/hr/10(7) cells. This value was several fold greater than the rate of production of deoxyadenosine by T cells (6 to 7 pmol/hr/10(7) cells). Deoxyadenosine synthesis required ribonucleotide reductase activity, and was maximal during the S-phase of the cell cycle. The T and B lymphoblasts formed relatively similar amounts of adenosine (870 to 1620 pmol/hr/10(7) cells) throughout the cell cycle. In ADA-deficient cells, a major fraction of the deoxyadenosine synthesized de novo was excreted into the extracellular space. These results establish that the endogenous synthesis and metabolism of deoxyadenosine (but not adenosine) is distinctly different in T and B lymphoblasts.
腺苷脱氨酶（ADA）基因缺陷与免疫缺陷疾病的关联突出了脱氧腺苷和腺苷代谢对人类淋巴细胞功能的重要性。然而，目前尚缺乏关于正常生长的人类T和B淋巴母细胞中脱氧腺苷和腺苷内源性产生及代谢的信息。在本实验中，我们使用了一系列嘌呤代谢中个别酶缺陷的细胞系，来定量人类T淋巴母细胞（CEM）、B淋巴母细胞（WI-L2）和组织细胞淋巴瘤细胞（DHL-9）中脱氧腺苷和腺苷的从头合成。B淋巴母细胞和组织细胞淋巴瘤细胞产生脱氧腺苷的速率为60至80 pmol/小时/10⁷个细胞。该值比T细胞产生脱氧腺苷的速率（6至7 pmol/小时/10⁷个细胞）高出几倍。脱氧腺苷的合成需要核糖核苷酸还原酶活性，并且在细胞周期的S期达到最大值。在整个细胞周期中，T和B淋巴母细胞形成的腺苷量相对相似（870至1620 pmol/小时/10⁷个细胞）。在ADA缺陷的细胞中，从头合成的大部分脱氧腺苷被分泌到细胞外空间。这些结果表明，T和B淋巴母细胞中脱氧腺苷（而非腺苷）的内源性合成和代谢明显不同。
