Expression of P2X(7) purinoceptors on human lymphocytes and monocytes: evidence for nonfunctional P2X(7) receptors |
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Authors: | Gu B J Zhang W Y Bendall L J Chessell I P Buell G N Wiley J S |
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Institution: | Department of Medicine, Nepean Hospital, University of Sydney, Penrith, New South Wales 2750, Australia. |
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Abstract: | Lymphocytes from normal subjects and patients with B-chroniclymphocytic leukemia (B-CLL) show functional responses to extracellular ATP characteristic of the P2X7 receptor (previously termedP2Z). These responses include opening of a cation-selectivechannel/pore that allows entry of the fluorescent dye ethidium andactivation of a membrane metalloprotease that sheds the adhesionmolecule L-selectin. The surface expression of P2X7receptors was measured in normal leucocytes, platelets, and B-CLLlymphocytes and correlated with their functional responses. Monocytesshowed four- to fivefold greater expression of P2X7 than B,T, and NK lymphocytes, whereas P2X7 expression onneutrophils and platelets was weak. All cell types demonstratedabundant intracellular expression of this receptor. All 12 subjectswith B-CLL expressed lymphocyte P2X7 at about the samelevel as B lymphocytes from normal subjects. P2X7 function, measured by ATP-induced uptake of ethidium, correlated closely withsurface expression of this receptor in normal and B-CLL lymphocytes andmonocytes (n = 47, r = 0.70; P< 0.0001). However, in three patients the ATP-induced uptake ofethidium into the malignant B lymphocytes was low or absent. The lackof P2X7 function in these B lymphocytes was confirmed bythe failure of ATP to induce Ba2+ uptake into theirlymphocytes. This lack of function of the P2X7 receptorresulted in a failure of ATP-induced shedding of L-selectin, anadhesion molecule that directs the recirculation of lymphocytes fromblood into the lymph node. |
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