BLOCKADE OF HUMAN P2X(7) RECEPTOR FUNCTION WITH A MONOCLONAL-ANTIBODY

A monoclonal antibody (MoAb) specific for the human P2X(7) receptor wa s generated in mice. As assessed by flow cytometry, the MoAb labeled h uman blood-derived macrophage cells natively expressing P2X(7) recepto rs and cells transfected with human P2X(7) but not other P2X receptor types. The MoAb was used to immunoprecipitate the human P2X(7) recepto r protein, and in immunohistochemical studies on human lymphoid tissue , P2X(7) receptor labeling was observed within discrete areas of the m arginal zone of human tonsil sections. The antibody also acted as a se lective antagonist of human P2X(7) receptors in several functional stu dies. Thus, whole cell currents, elicited by the brief application of 2',3'-(4-benzoyl)-benzoyl-ATP in cells expressing human P2X(7), were r educed in amplitude by the presence of the MoAb. Furthermore, preincub ation of human monocytic THP-1 cells with the MoAb antagonized the abi lity of P2X(7) agonists to induce the release of interleukin-1 beta. ( C) 1998 by The American Society of Hematology.