Expression of P2X(7) purinoceptors on human lymphocytes and monocytes: evidence for nonfunctional P2X(7) receptors.
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 Ba(2+) 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.
Gu
B J
BJ
Department of Medicine, Nepean Hospital, University of Sydney, Penrith, New South Wales 2750, Australia.
Zhang
W Y
WY
Bendall
L J
LJ
Chessell
I P
IP
Buell
G N
GN
Wiley
J S
JS
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001464:Barium / Q000493:pharmacokinetics; D001792:Blood Platelets / Q000378:metabolism; D004996:Ethidium / Q000493:pharmacokinetics; D005434:Flow Cytometry; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D019041:L-Selectin / Q000378:metabolism; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood*; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D058910:Purinergic P2 Receptor Agonists; D012333:RNA, Messenger / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000096:biosynthesis* / Q000235:genetics; D058486:Receptors, Purinergic P2X7; D012016:Reference Values
D000911:Antibodies, Monoclonal; C546468:P2RX7 protein, human; D058910:Purinergic P2 Receptor Agonists; D012333:RNA, Messenger; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; D019041:L-Selectin; D001464:Barium; C033901:3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate; D000255:Adenosine Triphosphate; D004996:Ethidium