Human ADA2 belongs to a new family of growth factors with adenosine deaminase activity
Human ADA2 belongs to a new family of growth factors with adenosine deaminase activity
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DOI：
10.1042/bj20050683
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发表时间：
2005-10-01
影响因子：
4.1
通讯作者：
Engström, A
中科院分区：
文献类型：
--
作者：
Zavialov, AV;Engström, A
在人类中发现了两种不同的 ADA（腺苷脱氨酶）同工酶 ADA1 和 ADA2。 ADA1 的遗传性突变会导致 SCID（严重联合免疫缺陷）。这一观察结果引发了对该酶结构和功能的广泛研究，揭示了它在淋巴细胞激活中的重要作用。相反，ADA2 的生理作用尚不清楚。 ADA2 在血清中的含量可以忽略不计，并且可能由单核细胞/巨噬细胞产生。在单核细胞/巨噬细胞被激活的各种疾病中，血清中的ADA2活性增加。在本研究中，我们报告 ADA2 是一种肝素结合蛋白。这使我们能够获得高度纯化的酶并研究其生物化学。 ADA2 被确定为一类新的 ADGF（ADA 相关生长因子）的成员，它存在于从果蝇到人类的几乎所有生物体中。我们的结果表明，ADA2 可能在缺氧期间的炎症部位和腺苷浓度显着升高且细胞外 pH 呈酸性的道岔生长区域具有活性。我们发现 ADA2 在市售制剂中与 IgG 共同纯化和浓缩，为使用此类制剂治疗导致非特异性免疫系统刺激的观察结果提供了有趣的解释。
Two distinct isoenzymes of ADA (adenosine deaminase), ADA1 and ADA2, have been found in humans. Inherited mutations in ADA1 result in SCID (severe combined immunodeficiency). This observation has led to extensive studies of the structure and function of this enzyme that have revealed an important role for it in lymphocyte activation. In contrast, the physiological role of ADA2 is unknown. ADA2 is found in negligible quantities in serum and may be produced by monocytes/macrophages. ADA2 activity in the serum is increased in various diseases in which monocyte/macrophage cells are activated. In the present study, we report that ADA2 is a heparin-binding protein. This allowed us to obtain a highly purified enzyme and to study its biochemistry. ADA2 was identified as a member of a new class of ADGFs (ADA-related growth factors), which is present in almost all organisms from flies to humans. Our results suggest that ADA2 may be active in sites of inflammation during hypoxia and in areas of turnout growth where the adenosine concentration is significantly elevated and the extracellular pH is acidic. Our finding that ADA2 co-purified and concentrated together with IgG in commercially available preparations offers an intriguing explanation for the observation that treatment with such preparations leads to non-specific immune-system stimulation.