期刊论文详细信息
BMC Immunology
P2 receptor mRNA expression profiles in human lymphocytes, monocytes and CD34+ stem and progenitor cells
David Erlinge1  Anders Bengtsson2  Sten Eirik W Jacobsen3  Lingwei Wang1 
[1]Department of Cardiology, Lund University Hospital, S-221 85 Lund, Sweden
[2]Department of Rheumatology, Lund University Hospital, S-221 85 Lund, Sweden
[3]Department of Hematopoietic Stem Cell Laboratory, Lund Center for Stem Cell Biology and Cell Therapy, Lund University Hospital, S-221 85 Lund, Sweden
关键词: hematopoietic stem cells;    CD34+ cells;    monocytes;    lymphocytes;    real-time PCR;    P2 receptor;   
Others  :  1078407
DOI  :  10.1186/1471-2172-5-16
 received in 2004-02-13, accepted in 2004-08-03,  发布年份 2004
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【 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.

【 授权许可】

   
2004 Wang et al; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Kunapuli SP, Daniel JL: P2 receptor subtypes in the cardiovascular system. Biochem J 1998, 336:513-523.
  • [2]Di Virgilio F, Chiozzi P, Ferrari D, Falzoni S, Sanz JM, Morelli A, Torboli M, Bolognesi G, Baricordi OR: Nucleotide receptors: an emerging family of regulatory molecules in blood cells. Blood 2001, 97:587-600.
  • [3]Sak K, Boeynaems JM, Everaus H: Involvement of P2Y receptors in the differentiation of haematopoietic cells. J Leukoc Biol 2003, 73:442-447.
  • [4]von Kugelgen I, Wetter A: Molecular pharmacology of P2Y-receptors. Naunyn Schmiedebergs Arch Pharmacol 2000, 362:310-323.
  • [5]Hollopeter G, Jantzen HM, Vincent D, Li G, England L, Ramakrishnan V, Yang RB, Nurden P, Nurden A, Julius D, Conley PB: Identification of the platelet ADP receptor targeted by antithrombotic drugs. Nature 2001, 409:202-207.
  • [6]Norenberg W, Illes P: Neuronal P2X receptors: localisation and functional properties. Naunyn Schmiedebergs Arch Pharmacol 2000, 362:324-339.
  • [7]Khakh BS, Burnstock G, Kennedy C, King BF, North RA, Seguela P, Voigt M, Humphrey PP: International union of pharmacology. XXIV. Current status of the nomenclature and properties of P2X receptors and their subunits. Pharmacol Rev 2001, 53:107-118.
  • [8]Wang L, Östberg O, Wihlborg AK, Brogren H, Jern S, Erlinge D: Quantification of ADP and ATP Receptor Expression in Human Platelets. J Thromb Haemost 2003, 1:330-336.
  • [9]Jneid H, Bhatt DL, Corti R, Badimon JJ, Fuster V, Francis GS: Aspirin and Clopidogrel in Acute Coronary Syndromes: Therapeutic Insights From the CURE Study. Arch Intern Med 2003, 163:1145-1153.
  • [10]CAPRIE: A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee. Lancet 1996, 348:1329-1339.
  • [11]van Furth R: Current view on the mononuclear phagocyte system. Immunobiology 1982, 161:178-185.
  • [12]Andreesen R, Bross KJ, Osterholz J, Emmrich F: Human macrophage maturation and heterogeneity: analysis with a newly generated set of monoclonal antibodies to differentiation antigens. Blood 1986, 67:1257-1264.
  • [13]Humphreys BD, Dubyak GR: Modulation of P2X7 nucleotide receptor expression by pro- and anti-inflammatory stimuli in THP-1 monocytes. J Leukoc Biol 1998, 64:265-273.
  • [14]Ferrari D, Stroh C, Schulze-Osthoff K: P2X7/P2Z purinoreceptor-mediated activation of transcription factor NFAT in microglial cells. J Biol Chem 1999, 274:13205-13210.
  • [15]Wang L, Karlsson L, Moses S, Hultgårdh-Nilsson A, Andersson M, Borna C, Gudbjartsson T, Jern S, Erlinge D: P2 Receptor Profiles in Human Vascular Smooth Muscle and Endothelial Cells. J Cardiovasc Pharmacol 2002, 40:841-853.
  • [16]Di Virgilio F, Borea PA, Illes P: P2 receptors meet the immune system. Trends Pharmacol Sci 2001, 22:5-7.
  • [17]Conigrave AD, Fernando KC, Gu B, Tasevski V, Zhang W, Luttrell BM, Wiley JS: P2Y(11) receptor expression by human lymphocytes: evidence for two cAMP-linked purinoceptors. Eur J Pharmacol 2001, 426:157-163.
  • [18]Vivekananthan DP, Bhatt DL, Chew DP, Chan AW, Moliterna DJ, Ellis SG, Topol E: Clopidogrel pretreatment prior to percutaneous coronary intervention attenuates periprocedural rise of C-reactive protein. J Am Coll Cardiol 2003, 41:1075-1165.
  • [19]Gargett CE, Wiley JS: The isoquinoline derivative KN-62 a potent antagonist of the P2Z-receptor of human lymphocytes. Br J Pharmacol 1997, 120:1483-1490.
  • [20]Sluyter R, Barden JA, Wiley JS: Detection of P2X purinergic receptors on human B lymphocytes. Cell Tissue Res 2001, 304:231-236.
  • [21]Jin J, Dasari VR, Sistare FD, Kunapuli SP: Distribution of P2Y receptor subtypes on haematopoietic cells. Br J Pharmacol 1998, 123:789-794.
  • [22]Wilkin F, Duhant X, Bruyns C, Suarez-Huerta N, Boeynaems JM, Robaye B: The P2Y11 receptor mediates the ATP-induced maturation of human monocyte-derived dendritic cells. J Immunol 2001, 166:7172-7177.
  • [23]Zhang FL, Luo L, Gustafson E, Palmer K, Qiao X, Fan X, Yang S, Laz TM, Bayne M, Monsma F., Jr.: P2Y(13): identification and characterization of a novel Galphai-coupled ADP receptor from human and mouse. J Pharmacol Exp Ther 2002, 301:705-713.
  • [24]Eschke D, Wust M, Hauschildt S, Nieber K: Pharmacological characterization of the P2X(7) receptor on human macrophages using the patch-clamp technique. Naunyn Schmiedebergs Arch Pharmacol 2002, 365:168-171.
  • [25]North RA: Molecular physiology of P2X receptors. Physiol Rev 2002, 82:1013-1067.
  • [26]Verfaillie CM: Hematopoietic stem cells for transplantation. Nat Immunol 2002, 3:314-317.
  • [27]Sitnicka E, Buza-Vidas N, Larsson S, Nygren JM, Liuba K, Jacobsen SE: Human CD34+ hematopoietic stem cells capable of multilineage engrafting NOD/SCID mice express flt3: distinct flt3 and c-kit expression and response patterns on mouse and candidate human hematopoietic stem cells. Blood 2003, 102:881-886.
  • [28]Wang L, Andersson M, Karlsson L, Watson MA, Cousens DJ, Jern S, Erlinge D: Increased mitogenic and decreased contractile P2 receptors in smooth muscle cells by shear stress in human vessels with intact endothelium. Arterioscler Thromb Vasc Biol 2003, 23:1370-1376.
  • [29]Borna C, Wang L, Gudbjartsson T, Karlsson L, Jern S, Malmsjo M, Erlinge D: Contractions in human coronary bypass vessels stimulated by extracellular nucleotides. Ann Thorac Surg 2003, 76:50-57.
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