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Inhibition of T3 Mediated T‐Cell Proliferation by Ca 2+ ‐Channel Blockers and Inhibitors of Ca 2+ /Phospholipid‐Dependent Kinase
Author(s) -
NEL A. E.,
DIRIENZO W.,
STEFANINI G. F.,
WOOTEN M. W.,
CAICA G. W.,
LATTANZE G. R.,
STEVENSON H. C.,
MILLER P.,
FUDENBERG H. H.,
GALBRAITH R. M.
Publication year - 1986
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/j.1365-3083.1986.tb02095.x
Subject(s) - trifluoperazine , kinase , calmodulin , phospholipid , microbiology and biotechnology , biochemistry , biology , chemistry , enzyme , membrane
The potential roles of Ca 2+ ions in the response of T lymphocytes to stimulation with monoclonal antisera to the T3 antigen were investigated by means of pharmacological agents that predominantly inhibit the flux of C a 2+ ions into cells (verapamil, nifedipine) or the activity of C a 2+ ‐dependent kinases (trifluoperazine, polymyxin B). As assessed by uptake of [ 3 H]thymidine. proliferation induced with anti T3‐recombinant IL‐2 at 72 h was inhibited by >80% in the presence of nifedipine at 50 μM, and almost completely arrested (>95% inhibition) with the other agents at the same concentration. Further quantitative assays of the effects of polymyxin B and trifluoperazine on C‐kinase labelling of exogenous substrate showed a major reduction with both agents, but inhibition was substantially greater with polymyxin B that with trifluoperazine (IC 50 = 14 and 70 μM respectively). These results were confirmed by qualitative assessment of C a 2+ /phospholipid‐dependent phosphorylation of endogenous substrates, which demonstrated major phosphoproteins of MW 56,000. 52.000, 43,000. and 20,000, and dose‐dependent reduction in labelling in the presence of polymyxin B. Similar results were obtained under more physiological conditions in intact cells labelled with 32 P orthophosphate. These findings indicate several possible roles for C a 2+ in T cell activation, and several possible levels of activity, including modulation of calmodulin‐dependent kinases and effects on C a 2+ /phospholipid‐dependent kinases and C a 2+ channels.