The potential importance of soluble deoxynucleotidase activity in mediating deoxyadenosine toxicity in human lymphoblasts.
The potential importance of soluble deoxynucleotidase activity in mediating deoxyadenosine toxicity in human lymphoblasts.
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DOI：
10.4049/jimmunol.126.1.348
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发表时间：
1981-01
影响因子：
4.4
通讯作者：
D. Carson;J. Kaye;D. Wasson
中科院分区：
文献类型：
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作者：
D. Carson;J. Kaye;D. Wasson
脱氧腺苷及其核苷酸与腺苷脱氨酶（ADA）遗传缺陷相关的免疫功能障碍的发病机制有关。我们以前已经表明，当用合成抑制剂阻断ADA时，人T淋巴母细胞样细胞系对脱氧腺苷毒性更敏感，脱氧腺苷核苷酸的去磷酸化速率较慢，并且具有比大多数B细胞系低得多的外-5 '-核苷酸酶水平。然而，淋巴细胞质膜外表面的酶似乎不太可能调节细胞内的脱氧核苷酸催化剂。我们现在报告说，人类淋巴母细胞也含有可溶性脱氧核苷酸酶活性，这是区别于质膜酶的几个标准。在不同来源和表型的多种人淋巴母细胞系中。可溶性脱氧核苷酸酶与对脱氧腺苷毒性的敏感性显著相关（rs = 0.80，p < 0.001）。
Deoxyadenosine and its nucleotides have been implicated in the pathogenesis of the immune dysfunction associated with a genetic deficiency of adenosine deaminase (ADA). We have previously shown that when ADA is blocked with a synthetic inhibitor, human T lymphoblastoid cell lines are more sensitive to deoxyadenosine toxicity, dephosphorylate deoxyadenosine nucleotides at a slower rate, and have much lower levels of ecto-5'-nucleotidase than most B cell lines. It seemed unlikely, however, that an enzyme on the outer surface of the lymphocyte plasma membrane could regulate intracellular deoxynucleotide catabolism. We now report that human lymphoblasts also contain a soluble deoxynucleotidase activity that is distinguishable from the plasma membrane enzyme by several criteria. In multiple human lymphoblastoid cell lines of varying origin and phenotype. soluble deoxynucleotidase correlated significantly (rs = 0.80, p < 0.001) with sensitivity to deoxyadenosine toxicity.