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An ATP-activated channel is involved in mitogenic stimulation of human T
lymphocytes
OR Baricordi, D Ferrari, L Melchiorri, P Chiozzi, S Hanau, E Chiari, M Rubini and F Di Virgilio
Department of Biochemistry and Molecular Biology, University of Ferrara,
Italy.
We investigated the effect of pharmacologic modulation of the ATP receptor
on intracellular ion changes and proliferative response of human peripheral
blood lymphocytes (PBLs) and purified T lymphocytes. Extracellular ATP
(ATPe) triggered in these cells an increase in the cytoplasmic Ca2+
concentration ([Ca2+]i) and plasma membrane depolarization. Whereas both
Ca2+ release from intracellular stores and influx across the plasma
membrane were detected in the whole PBL population, only Ca2+ influx was
observed in T cells. In the presence of near physiologic extracellular Na+
concentrations (125 mmol/L), Ca2+ permeability through the ATPe-gated
channel was very low, suggesting a higher selectivity for monovalent over
divalent cations. The selective P2Z agonist benzoylbenzoic ATP (BzATP)
increased [Ca2+]i in the presence but not the absence of extracellular Ca2+
and also caused plasma membrane depolarization. The covalent blocker
oxidized ATP (oATP), an inhibitor of P2X and P2Z receptors, prevented Ca2+
influx and plasma membrane depolarization, but had no effect on Ca2+
release from stores. Stimulation with ATPe alone had no significant effects
on PBL 3H-thymidine incorporation. On the contrary, ATPe or BzATP had a
synergistic effect on DNA synthesis stimulated by selective T-cell mitogens
such as phytohemagglutinin, anti-CD3 monoclonal antibody, or allogenic PBLs
(mixed lymphocyte cultures). Treatment with oATP inhibited mitogenic
stimulation by these receptor-directed agents but not by the combined
application of the Ca2+ ionophore ionomycin and phorbol myristate acetate.
Interleukin-2 partially relieved inhibition by oATP. These results suggest
that human T lymphocytes express a plasma membrane channel gated by ATPe
that is involved in mitogenic stimulation.
Volume 87,
Issue 2,
pp. 682-690,
01/15/1996
Copyright © 1996 by The American Society of Hematology
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