Blockade of human P2X7 receptor function with a monoclonal antibody.
A monoclonal antibody (MoAb) specific for the human P2X7 receptor was generated in mice. As assessed by flow cytometry, the MoAb labeled human blood-derived macrophage cells natively expressing P2X7 receptors and cells transfected with human P2X7 but not other P2X receptor types. The MoAb was used to immunoprecipitate the human P2X7 receptor protein, and in immunohistochemical studies on human lymphoid tissue, P2X7 receptor labeling was observed within discrete areas of the marginal zone of human tonsil sections. The antibody also acted as a selective antagonist of human P2X7 receptors in several functional studies. Thus, whole cell currents, elicited by the brief application of 2',3'-(4-benzoyl)-benzoyl-ATP in cells expressing human P2X7, were reduced in amplitude by the presence of the MoAb. Furthermore, preincubation of human monocytic THP-1 cells with the MoAb antagonized the ability of P2X7 agonists to induce the release of interleukin-1beta.
Buell
G
G
Glaxo Institute for Molecular Biology, Geneva, Switzerland; and the Glaxo Institute for Applied Pharmacology, Department of Pharmacology, University of Cambridge, Cambridge, UK.
Chessell
I P
IP
Michel
A D
AD
Collo
G
G
Salazzo
M
M
Herren
S
S
Gretener
D
D
Grahames
C
C
Kaur
R
R
Kosco-Vilbois
M H
MH
Humphrey
P P
PP
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D007948:Leukemia, Monocytic, Acute / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D014066:Palatine Tonsil / Q000166:cytology / Q000276:immunology; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2 / Q000276:immunology; D058486:Receptors, Purinergic P2X7; D015290:Second Messenger Systems / Q000502:physiology
D000911:Antibodies, Monoclonal; D007375:Interleukin-1; C546468:P2RX7 protein, human; C546469:P2rx7 protein, mouse; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; C033901:3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate; D000255:Adenosine Triphosphate