Expression of P2 receptors at sites of chronic inflammation.

Extracellular nucleotides have been identified as important signaling molecules. These nucleotides act on the P2 family of receptors that respond by either forming an ion-channel or by activation of a signal transduction cascade, both of which enable a cellular response. Although a role for P2 receptors in inflammation has been implied, the local expression pattern and kinetics of these receptors at sites of inflammation are not known. Therefore, we have studied the expression of the P2 receptors expressed by inflammatory cells or by cells in the vasculature, with special attention of P2X(1), P2X(7)R, P2Y(1)R, and P2Y(2)R. As a suitable model for studying inflammatory reactions, we have employed the foreign body reaction (FBR), a sterile inflammatory reaction induced by implanting degradable cross-linked dermal sheep collagen disks subcutaneously in the rat. We show that, in the vasculature, the express of P2X(7)R, P2Y(1)R and P2Y(2)R increase until day 2. The expression of P2X(7)R and P2Y(1)R on macrophages and giant cells increased during the course of the inflammatory reaction which was studied for 21 days. The expression of the P2Y(2)R on macrophages and giant cells inside the foreign body increases with time, whereas the expression on macrophages in the surrounding tissue is maximal at day 5. The expression of P2X(1)R remains at a constant low level. The upregulation of P2X(7)R, P2Y(1)R, and P2Y(2)R over time suggests a regulatory function for these receptors in inflammation.