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Cyclosporine A inhibits Ca2+-dependent stimulation of the Na+/H+ antiport in human T cells.

dc.contributor.author Rosoff, Philip Martin
dc.contributor.author Terres, G
dc.coverage.spatial United States
dc.date.accessioned 2015-12-03T14:30:24Z
dc.date.issued 1986-08
dc.identifier http://www.ncbi.nlm.nih.gov/pubmed/3015982
dc.identifier.issn 0021-9525
dc.identifier.uri https://hdl.handle.net/10161/10958
dc.description.abstract The cyclic undecapeptide cyclosporine A (CsA) is a potent immunosuppressive agent that inhibits the initial activation of T lymphocytes. This agent appears to be most effective in blocking the action of mitogens such as concanavalin A and the calcium ionophore A23187, which cause an influx of Ca2+, but not those that may act by alternate mechanisms. These observations suggest that CsA may block a Ca2+-dependent step in T cell activation. We have shown that stimulation of the T3-T cell receptor complex-associated Ca2+ transporter activates the Na+/H+ antiport (Rosoff, P. M., and L. C. Cantley, 1985, J. Biol. Chem., 260: 14053-14059). The tumor-promoting phorbol esters, which are co-mitogenic for T cells, activate the exchanger by a separate pathway which is mediated by protein kinase C. Both the rise in intracellular Ca2+ and intracellular pH may be necessary for the successful triggering of cellular activation. In this report we show that CsA blocks the T3-T cell receptor-stimulated, Ca2+ influx-dependent activation of Na+/H+ exchange, but not the phorbol ester-mediated pathway in a transformed human T cell line. CsA inhibited mitogen-stimulation of interleukin-2 production in a separate cell line. CsA also inhibited vasopressin stimulation of the antiporter in normal rat kidney fibroblasts, but had no effect on serum or 12-O-tetradecanoyl phorbol 13-acetate stimulation. CsA did not affect serum or vasopressin or serum stimulation of normal rat kidney cell proliferation. CsA also had no effect on lipopolysaccharide or phorbol ester stimulation of Na+/H+ exchange activity or induction of differentiation in 70Z/3 pre-B lymphocytes in which these events are initiated by the protein kinase C pathway. These data suggest that mechanisms of activation of Na+/H+ exchange that involve an elevation in cytosolic Ca2+ are blocked by CsA but that C kinase-mediated regulation is unaffected. The importance of the Na+/H+ antiport in the regulation of growth and differentiation of T cells is discussed.
dc.language eng
dc.relation.ispartof J Cell Biol
dc.subject B-Lymphocytes
dc.subject Calcium
dc.subject Carrier Proteins
dc.subject Cell Differentiation
dc.subject Cell Line
dc.subject Cyclosporins
dc.subject Fibroblasts
dc.subject Humans
dc.subject Hydrogen-Ion Concentration
dc.subject In Vitro Techniques
dc.subject Interleukin-2
dc.subject Lymphocyte Activation
dc.subject Mitogens
dc.subject Receptors, Antigen, T-Cell
dc.subject Sodium
dc.subject Sodium-Hydrogen Antiporter
dc.subject T-Lymphocytes
dc.title Cyclosporine A inhibits Ca2+-dependent stimulation of the Na+/H+ antiport in human T cells.
dc.type Journal article
pubs.author-url http://www.ncbi.nlm.nih.gov/pubmed/3015982
pubs.begin-page 457
pubs.end-page 463
pubs.issue 2
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Duke
pubs.organisational-group Medicine
pubs.organisational-group Medicine, Medical Oncology
pubs.organisational-group Pediatrics
pubs.organisational-group Pediatrics, Hematology-Oncology
pubs.organisational-group School of Medicine
pubs.publication-status Published
pubs.volume 103


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