P2 receptor mRNA expression profiles in human lymphocytes, monocytes and CD34+ stem and progenitor cells

Extracellular nucleotides (ATP, ADP, UTP and UDP) exert a wide range of biological effects in blood cells mediated by multiple ionotropic P2X receptors and G protein-coupled P2Y receptors. Although pharmacological experiments have suggested the presence of several P2 receptor subtypes on monocytes and lymphocytes, some results are contradictory. Few physiological functions have been firmly established to a specific receptor subtype, partly because of a lack of truly selective agonists and antagonists. This stimulated us to investigate the expression of P2X and P2Y receptors in human lymphocytes and monocytes with a newly established quantitative mRNA assay for P2 receptors. In addition, we describe for the first time the expression of P2 receptors in CD34⁺ stem and progenitor cells implicating a potential role of P2 receptors in hematopoietic lineage and progenitor/stem cell function.

Using a quantitative mRNA assay, we assessed the hypothesis that there are specific P2 receptor profiles in inflammatory cells. The P2X₄ receptor had the highest expression in lymphocytes and monocytes. Among the P2Y receptors, P2Y₁₂ and P2Y₂ had highest expression in lymphocytes, while the P2Y₂ and P2Y₁₃ had highest expression in monocytes. Several P2 receptors were expressed (P2Y₂, P2Y₁, P2Y₁₂, P2Y₁₃, P2Y₁₁, P2X₁, P2X₄) in CD34+ stem and progenitor cells.

The most interesting findings were the high mRNA expression of P2Y₁₂ receptors in lymphocytes potentially explaining the anti-inflammatory effects of clopidogrel, P2Y₁₃ receptors in monocytes and a previously unrecognised expression of P2X₄ in lymphocytes and monocytes. In addition, for the first time P2 receptor mRNA expression patterns was studied in CD34⁺ stem and progenitor cells. Several P2 receptors were expressed (P2Y₂, P2Y₁, P2Y₁₂, P2Y₁₃, P2Y₁₁, P2X₁, P2X₄), indicating a role in differentiation and proliferation. Thus, it is possible that specific antibodies to P2 receptors could be used to identify progenitors for monocytes, lymphocytes and megakaryocytes.