Expression of multiple ATP receptor subtypes during the differentiation and inflammatory activation of myeloid leukocytes

Abstract

ATP can activate both G-protein-coupled signaling systems or ATP-gated channels by stimulating either P2Y-family or P2X-family receptors. Our studies indicate that different P2Y- and P2X-family receptors are expressed in mature human phagocytic leukocytes and in myeloid progenitor cells. The P2Y1 receptor is functionally expressed only in early myeloid progenitor cells, whereas the P(2U)/P2Y2 receptor is expressed in fate-stage progenitor cells and in mature monocytes and neutrophils. The P2X1 receptor is not expressed in early myeloid progenitors, but it is abundantly expressed when these cells commit to monocytic differentiation. However, the expression of P2X1 and P(2U)/P2Y2 receptors is significantly down-regulated when myeloid leukocytes are activated with proinflammatory cytokines. In contrast, these same inflammatory stimuli induce a large up-regulation of P2Z/P2X7 receptor expression. We propose that the differential expression of ATP receptor subtypes in various myeloid leukocyte populations indicates that these cells utilize locally released ATP and particular ATP receptors for distinct types of autocrine and paracrine communication.