Regulation of adenosine receptor engagement by ecto-adenosine deaminase
Regulation of adenosine receptor engagement by ecto-adenosine deaminase
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DOI：
10.1096/fj.03-0011fje
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发表时间：
2004-01-01
期刊：
影响因子：
4.8
通讯作者：
Thompson, LF
中科院分区：
文献类型：
--
作者：
Hashikawa, T;Hooker, SW;Thompson, LF
腺苷脱氨酶 (ADA) 可以通过与 CD26 的相互作用定位到细胞表面。使用 CD26 转染的细胞，我们证明细胞表面 ADA (ecto-ADA) 可以通过将细胞外腺苷 (Ado) 降解为肌苷来调节腺苷受体的结合。这种能力取决于 CD26 表达、ecto-ADA 的 CD26 饱和程度以及 cAMP 反应的动力学。因此，当 CD26 转染的细胞与外源 ADA 一起孵育以增加 ecto-ADA 表达时，cAMP 反应显着降低。通过使用特定的 ADA 抑制剂 2'-脱氧考福霉素进行治疗，证明了 ecto-ADA 抑制 cAMP 反应的能力。这抑制了 ecto-ADA 降解 Ado 的能力并增加了 cAMP 反应。尽管与 CD26 转染细胞相比，人胸腺细胞上的 CD26 表达较低，但它已被 ecto-ADA 饱和。当以高密度孵育的胸腺细胞（以模拟组织中的情况）暴露于外源腺苷时，ecto-ADA 会显着降低 cAMP 反应。我们得出的结论是，ecto-ADA 具有在体内调节腺苷受体介导的 cAMP 反应的潜力，在具有 CD26(+) 细胞的组织中，以及由凋亡或炎症引起的足够的细胞死亡，为与 CD26 结合的 ADA 提供了来源。
Adenosine deaminase (ADA) can localize to the cell surface through its interaction with CD26. Using CD26-transfected cells, we demonstrate that cell surface ADA (ecto-ADA) can regulate adenosine receptor engagement by degrading extracellular adenosine (Ado) to inosine. This ability was dependent upon CD26 expression, the extent of CD26 saturation with ecto-ADA, and the kinetics of the cAMP response. Thus, the cAMP response was markedly decreased when CD26-transfected cells were incubated with an exogenous source of ADA to increase ecto-ADA expression. The ability of ecto-ADA to inhibit the cAMP response was demonstrated by treatment with the specific ADA inhibitor 2'-deoxycoformycin. This inhibited the ability of ecto-ADA to degrade Ado and increased the cAMP response. Although CD26 expression on human thymocytes was low compared with that of CD26-transfected cells, it was saturated with ecto-ADA. When thymocytes incubated at high densities (to mimic the situation in tissues) were exposed to exogenous adenosine, the cAMP response was dramatically decreased by ecto-ADA. We conclude that ecto-ADA has the potential to regulate adenosine receptor-mediated cAMP responses in vivo in tissues with CD26(+) cells and sufficient cell death caused by apoptosis or inflammation to provide a source of ADA to bind to CD26.