Zavialov Andrey V, Engström Ake
Institute of Immunological Engineering, 142380 Lyubuchany, Moscow Region, Russia.
Biochem J. 2005 Oct 1;391(Pt 1):51-7. doi: 10.1042/BJ20050683.
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 tumour 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.
人类体内已发现两种不同的腺苷脱氨酶（ADA）同工酶，即ADA1和ADA2。ADA1的遗传性突变会导致严重联合免疫缺陷（SCID）。这一观察结果促使人们对该酶的结构和功能进行了广泛研究，揭示了其在淋巴细胞活化中的重要作用。相比之下，ADA2的生理作用尚不清楚。血清中ADA2的含量极少，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活性会增加。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该酶并研究其生物化学性质。ADA2被鉴定为一类新的ADA相关生长因子（ADGFs）的成员，这类因子几乎存在于从果蝇到人类的所有生物体中。我们的结果表明，ADA2可能在缺氧时的炎症部位以及肿瘤生长区域（腺苷浓度显著升高且细胞外pH呈酸性）发挥作用。我们发现，在市售制剂中ADA2与IgG共纯化并浓缩，这为使用此类制剂治疗会导致非特异性免疫系统刺激这一观察结果提供了一个有趣的解释。
