Chused T M, Apasov S, Sitkovsky M
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20852, USA.
J Immunol. 1996 Aug 15;157(4):1371-80.
Murine T, but not B, lymphocytes constitutively express a membrane receptor for adenosine nucleotides that opens a nonspecific pore that admits Ca2+ and ethidium (314 Da), but not propidium (415 Da) ions. ATP, ADP, and AMP show decreasing potency; UTP and adenosine are inactive. Nonhydrolyzable ATP analogues are completely ineffective. Oxidized ATP inhibits the response. Activity is detectable at ATP concentrations of 125 microM and peaks at 1 mM. The intracellular free Ca2+ ([Ca2+]i) rise is not reversed by removing ATP by centrifugation or apyrase. The kinetics, agonist and antagonist profiles, and the passage of ions as large as ethidium are the characteristics of a P2z-type purinoceptor. No expression of classical P2x-, P2u-, or P2Y-type purinoceptors can be detected. The [Ca2+]i elevating activity of the ATP receptor is modulated during T cell differentiation. CD4+8+ double-positive thymocytes are the least responsive. CD4-8+ single-positive thymocytes, CD8+ splenic T cells, CD4+8- single-positive thymocytes, and CD4+ splenic T cells show increasing reactivity. Measurement of P2Z expression by the rate of ethidium ion uptake correlates with the [Ca2+]i. The trimodal expression of P2Z by splenic CD4+ T cells correlates with the subsets defined by CD44 and CD45RB, differentiation Ags that distinguish memory cells: P2Zlow cells are CD44brightCD45RBbright; P2Zint are CD44dullCD45RBint; P2Zhigh are CD44brightCD45RBdull. It is suggested that P2Z receptor-mediated signaling could be involved in the regulation of differentiation and cell death in the thymus and peripheral T lymphocytes.
小鼠T淋巴细胞而非B淋巴细胞组成性表达一种腺苷核苷酸膜受体，该受体可打开一个非特异性孔道，允许Ca2+和溴乙锭（314 Da）进入，但不允许碘化丙啶（415 Da）离子进入。ATP、ADP和AMP的效力逐渐降低；UTP和腺苷无活性。不可水解的ATP类似物完全无效。氧化型ATP抑制该反应。在ATP浓度为125 μM时可检测到活性，在1 mM时达到峰值。通过离心或腺苷三磷酸双磷酸酶去除ATP并不能逆转细胞内游离Ca2+（[Ca2+]i）的升高。其动力学、激动剂和拮抗剂特征以及像溴乙锭这样大的离子的通过情况是P2z型嘌呤受体的特点。未检测到经典P2x、P2u或P2Y型嘌呤受体的表达。ATP受体的[Ca2+]i升高活性在T细胞分化过程中受到调节。CD4+8+双阳性胸腺细胞反应性最低。CD4-8+单阳性胸腺细胞、CD8+脾T细胞、CD4+8-单阳性胸腺细胞和CD4+脾T细胞的反应性逐渐增加。通过溴乙锭离子摄取速率测量P2Z表达与[Ca2+]i相关。脾CD4+ T细胞中P2Z的三峰表达与由CD44和CD45RB定义的亚群相关，CD44和CD45RB是区分记忆细胞的分化抗原：P2Z低表达细胞为CD44亮CD45RB亮；P2Z中等表达细胞为CD44暗CD45RB中等；P2Z高表达细胞为CD44亮CD45RB暗。提示P2Z受体介导的信号传导可能参与胸腺和外周T淋巴细胞分化及细胞死亡的调节。
