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Blood, Vol. 92 No. 10 (November 15), 1998:
pp. 3521-3528
RAPID COMMUNICATION
Blockade of Human P2X7 Receptor Function With a Monoclonal
Antibody
G. Buell,
I.P. Chessell,
A.D. Michel,
G. Collo,
M. Salazzo,
S. Herren,
D. Gretener,
C. Grahames,
R. Kaur,
M.H. Kosco-Vilbois, and
P.P.A. Humphrey
From the Glaxo Institute for Molecular Biology, Geneva, Switzerland;
and the Glaxo Institute for Applied Pharmacology, Department of
Pharmacology, University of Cambridge, Cambridge, UK.
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-1 .
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