Expression of P2X7 purinoceptors on human lymphocytes and monocytes:: evidence for nonfunctional P2X7 receptors
Expression of P2X7 purinoceptors on human lymphocytes and monocytes:: evidence for nonfunctional P2X7 receptors
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DOI：
10.1152/ajpcell.2000.279.4.c1189
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发表时间：
2000-10-01
影响因子：
5.5
通讯作者：
Wiley, JS
中科院分区：
文献类型：
--
作者：
Gu, BJ;Zhang, WY;Wiley, JS
来自正常受试者和 B 慢性淋巴细胞白血病 (B-CLL) 患者的淋巴细胞显示出对 P2X(7) 受体（以前称为 P2Z）特征的细胞外 ATP 的功能反应。这些反应包括打开阳离子选择性通道/孔，允许荧光染料乙锭进入，以及激活膜金属蛋白酶，释放粘附分子 L-选择素。在正常白细胞、血小板和 B-CLL 淋巴细胞中测量 P2X(7) 受体的表面表达，并与其功能反应相关。单核细胞的 P2X(7) 表达比 B、T 和 NK 淋巴细胞高四到五倍，而中性粒细胞和血小板上的 P2X(7) 表达较弱。所有细胞类型均表现出该受体的丰富细胞内表达。所有 12 名 B-CLL 受试者表达的淋巴细胞 P2X(7) 水平与正常受试者的 B 淋巴细胞大致相同。通过 ATP 诱导的乙锭摄取来测量的 P2X(7) 功能与正常和 B-CLL 淋巴细胞和单核细胞中该受体的表面表达密切相关 (n = 47，r = 0.70；P < 0.0001)。然而，在三名患者中，ATP 诱导的恶性 B 淋巴细胞对乙锭的摄取较低或不存在。 ATP 未能诱导 Ba2+ 摄取到淋巴细胞中，证实了这些 B 淋巴细胞中缺乏 P2X(7) 功能。 P2X(7) 受体功能的缺乏导致 ATP 诱导的 L-选择素脱落失败，L-选择素是一种指导淋巴细胞从血液再循环到淋巴结的粘附分子。
Lymphocytes from normal subjects and patients with B-chronic lymphocytic leukemia (B-CLL) show functional responses to extracellular ATP characteristic of the P2X(7) receptor (previously termed P2Z). These responses include opening of a cation-selective channel/pore that allows entry of the fluorescent dye ethidium and activation of a membrane metalloprotease that sheds the adhesion molecule L-selectin. The surface expression of P2X(7) receptors was measured in normal leucocytes, platelets, and B-CLL lymphocytes and correlated with their functional responses. Monocytes showed four- to fivefold greater expression of P2X(7) than B, T, and NK lymphocytes, whereas P2X(7) expression on neutrophils and platelets was weak. All cell types demonstrated abundant intracellular expression of this receptor. All 12 subjects with B-CLL expressed lymphocyte P2X(7) at about the same level as B lymphocytes from normal subjects. P2X(7) function, measured by ATP-induced uptake of ethidium, correlated closely with surface expression of this receptor in normal and B-CLL lymphocytes and monocytes (n = 47, r = 0.70; P< 0.0001). However, in three patients the ATP-induced uptake of ethidium into the malignant B lymphocytes was low or absent. The lack of P2X(7) function in these B lymphocytes was confirmed by the failure of ATP to induce Ba2+ uptake into their lymphocytes. This lack of function of the P2X(7) receptor resulted in a failure of ATP-induced shedding of L-selectin, an adhesion molecule that directs the recirculation of lymphocytes from blood into the lymph node.