Role of p2 nucleotide receptors in inflammation and hematopoiesis

Extracellular ATP and other nucleotides elicit functional responses in many cell types by activating either G-protein coupled receptors (P2Y class) or ionotropic ATP-gated channel receptors (P2X class). We and others have investigated the expression and function of multiple P2 receptors in leukocytes of the inflammatory system and in their hematopoietic progenitors. These studies indicate that at least seven P2 receptor subtypes belonging to both the P2Y and P2X classes are differentially expressed in mature inflammatory leukocyte subpopulations and in myeloid progenitor cells. Moreover, the expression of certain P2 receptors is rapidly down-regulated, while others are upregulated, when myeloid leukocytes are treated with various inflammatory cytokines or hematopoietic growth factors. This differential expression of P2 receptor subtypes in various leukocyte subpopulations indicates that inflammatory leukocytes use locally released ATP and particular P2 receptors for distinct types of autocrine/paracrine communication. This presentation will focus on recent findings or hypotheses regarding: (i) the factors that regulate expression of P2 receptor subtypes during inflammatory activation of leukocytes; (ii) the role of particular P2 receptors in cytokine release and in leukocyte death; and (iii) the release and processing of extracellular nucleotides during inter-cellular signaling among inflammatory cell types.