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

被引:105
作者
Wang L. [1 ]
Jacobsen S.E.W. [2 ]
Bengtsson A. [3 ]
Erlinge D. [1 ]
机构
[1] Department of Cardiology, Lund University Hospital
[2] Department of Hematopoietic Stem Cell Laboratory, Lund Center for Stem Cell Biology and Cell Therapy, Lund University Hospital
[3] Department of Rheumatology, Lund University Hospital
关键词
CD34[!sup]+[!/sup] cells; Hematopoietic stem cells; Lymphocytes; Monocytes; P2; receptor; Real-time PCR;
D O I
10.1186/1471-2172-5-16
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学科分类号
摘要
Background: 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. Results: 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. Conclusions: 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. © 2004 Wang et al; licensee BioMed Central Ltd.
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共 29 条
[1]  
Kunapuli S.P., Daniel J.L., P2 receptor subtypes in the cardiovascular system, Biochem. J., 336, pp. 513-523, (1998)
[2]  
Di Virgilio F., Chiozzi P., Ferrari D., Falzoni S., Sanz J.M., Morelli A., Torboli M., Bolognesi G., Baricordi O.R., Nucleotide receptors: An emerging family of regulatory molecules in blood cells, Blood, 97, pp. 587-600, (2001)
[3]  
Sak K., Boeynaems J.M., Everaus H., Involvement of P2Y receptors in the differentiation of haematopoietic cells, J. Leukoc. Biol., 73, pp. 442-447, (2003)
[4]  
von Kugelgen I., Wetter A., Molecular pharmacology of P2Y-receptors, Naunyn Schmiedebergs Arch. Pharmacol., 362, pp. 310-323, (2000)
[5]  
Hollopeter G., Jantzen H.M., Vincent D., Li G., England L., Ramakrishnan V., Yang R.B., Nurden P., Nurden A., Julius D., Conley P.B., Identification of the platelet ADP receptor targeted by antithrombotic drugs, Nature, 409, pp. 202-207, (2001)
[6]  
Norenberg W., Illes P., Neuronal P2X receptors: Localisation functional properties, Naunyn Schmiedebergs Arch. Pharmacol., 362, pp. 324-339, (2000)
[7]  
Khakh B.S., Burnstock G., Kennedy C., King B.F., North R.A., Seguela P., Voigt M., Humphrey P.P., International union of pharmacology. XXIV. Current status of the nomenclature properties of P2X receptors their subunits, Pharmacol. Rev., 53, pp. 107-118, (2001)
[8]  
Wang L. Ostberg O., Wihlborg A.K., Brogren H., Jern S., Erlinge D., Quantification of ADP ATP Receptor Expression in Human Platelets, J. Thromb. Haemost., 1, pp. 330-336, (2003)
[9]  
Jneid H., Bhatt D.L., Corti R., Badimon J.J., Fuster V., Francis G.S., Aspirin Clopidogrel in Acute Coronary Syndromes: Therapeutic Insights From the CURE Study, Arch. Intern. Med., 163, pp. 1145-1153, (2003)
[10]  
CAPRIE: A randomised blinded trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE), Lancet, 348, pp. 1329-1339, (1996)