An ATP-Activated Channel Is Involved in Mitogenic Stimulation of Human T Lymphocytes

作者: OR Baricordi , D Ferrari , L Melchiorri , P Chiozzi , S Hanau

DOI: 10.1182/BLOOD.V87.2.682.BLOODJOURNAL872682

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摘要: We investigated the effect of pharmacologic modulation ATP receptor on intracellular ion changes and proliferative response human peripheral blood lymphocytes (PBLs) purified T lymphocytes. Extracellular (ATPe) triggered in these cells an increase cytoplasmic Ca2+ concentration ([Ca2+]i) plasma membrane depolarization. Whereas both release from stores influx across were detected whole PBL population, only was observed cells. In presence near physiologic extracellular Na+ concentrations (125 mmol/L), permeability through ATPe-gated channel very low, suggesting a higher selectivity for monovalent over divalent cations. The selective P2Z agonist benzoylbenzoic (BzATP) increased [Ca2+]i but not absence also caused covalent blocker oxidized (oATP), inhibitor P2X receptors, prevented depolarization, had no stores. Stimulation with ATPe alone significant effects 3H-thymidine incorporation. On contrary, or BzATP synergistic DNA synthesis stimulated by T-cell mitogens such as phytohemagglutinin, anti-CD3 monoclonal antibody, allogenic PBLs (mixed lymphocyte cultures). Treatment oATP inhibited mitogenic stimulation receptor-directed agents combined application ionophore ionomycin phorbol myristate acetate. Interleukin-2 partially relieved inhibition oATP. These results suggest that express gated is involved stimulation.

参考文章(38)
F Di Virgilio, C Fasolato, T H Steinberg, Inhibitors of membrane transport system for organic anions block fura-2 excretion from PC12 and N2A cells Biochemical Journal. ,vol. 256, pp. 959- 963 ,(1988) , 10.1042/BJ2560959
S. Ikehara, R. N. Pahwa, D. G. Lunzer, R. A. Good, Mukund Modak, Adenosine-5'-triphosphate-(ATP) mediated stimulation and suppression of DNA synthesis in lymphoid cells. I. Characterization of ATP responsive cells in mouse lymphoid organs. Journal of Immunology. ,vol. 127, pp. 1834- 1838 ,(1981)
C Fasolato, T Pozzan, P Pizzo, Receptor-mediated calcium influx in PC12 cells. ATP and bradykinin activate two independent pathways. Journal of Biological Chemistry. ,vol. 265, pp. 20351- 20355 ,(1990) , 10.1016/S0021-9258(17)30510-0
R. G. Kemp, J. Lin, Rajabather Krishnaraj, Exogenous ATP enhances calcium influx in intact thymocytes. Journal of Immunology. ,vol. 135, pp. 3403- 3410 ,(1985)
A Filippini, R E Taffs, T Agui, M V Sitkovsky, Ecto-ATPase activity in cytolytic T-lymphocytes. Protection from the cytolytic effects of extracellular ATP. Journal of Biological Chemistry. ,vol. 265, pp. 334- 340 ,(1990) , 10.1016/S0021-9258(19)40234-2
T H Steinberg, A S Newman, J A Swanson, S C Silverstein, ATP4- permeabilizes the plasma membrane of mouse macrophages to fluorescent dyes. Journal of Biological Chemistry. ,vol. 262, pp. 8884- 8888 ,(1987) , 10.1016/S0021-9258(18)47497-2
C M Roifman, A Cohen, S Padeh, ATP-induced activation of human B lymphocytes via P2-purinoceptors. Journal of Immunology. ,vol. 146, pp. 1626- 1632 ,(1991)
J R Ortaldo, A Schmidt, R B Herberman, Inhibition of human natural killer cell reactivity by exogenous adenosine 5'-triphosphate. Journal of Immunology. ,vol. 132, pp. 146- 150 ,(1984)