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. 1993 Jul 15;293(Pt 2):395–398. doi: 10.1042/bj2930395

Two independently regulated Ca2+ entry mechanisms coexist in Jurkat T cells during T cell receptor antigen activation.

S C Chow 1, G E Kass 1, S Orrenius 1
PMCID: PMC1134373  PMID: 8343120

Abstract

Receptor-mediated Ca2+ influx was studied in the human leukaemic T cell line, Jurkat. Stimulation of these cells through the T cell antigen-receptor complex with OKT3 (an antibody against the CD3 molecules of the T cell antigen-receptor complex), or inhibition of the endoplasmic reticular Ca(2+)-ATPase with thapsigargin, resulted in Ca2+ mobilization from intracellular stores and the activation of Ca2+ and Mn2+ entry. The rates of thapsigargin-induced Ca2+ and Mn2+ entry in Jurkat cells were 76% and 64% respectively of those observed after treatment of these cells with OKT3. The combined addition of thapsigargin plus OKT3 to Jurkat cells produced an enhanced effect on the sustained increase in the cytosolic free Ca2+ concentration that was greater than that obtained by addition of thapsigargin or OKT3 alone. The rates of Ca2+ and Mn2+ entry were increased to 119% and 112% respectively of the OKT3-induced rates. Taken together, these results suggest that the inositol 1,4,5-trisphosphate-sensitive Ca(2+)-pool-dependent bivalent cation entry only accounts for 57% and 52% respectively of the total OKT3-dependent Ca2+ and Mn2+ entry, and that the rest is mediated by second messenger(s). Thus two separate pathways coexist in regulating Ca2+ entry in Jurkat cells during activation mediated through the T cell receptor.

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Selected References

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  1. Abdel-Latif A. A. Calcium-mobilizing receptors, polyphosphoinositides, and the generation of second messengers. Pharmacol Rev. 1986 Sep;38(3):227–272. [PubMed] [Google Scholar]
  2. Benham C. D., Tsien R. W. A novel receptor-operated Ca2+-permeable channel activated by ATP in smooth muscle. Nature. 1987 Jul 16;328(6127):275–278. doi: 10.1038/328275a0. [DOI] [PubMed] [Google Scholar]
  3. Berridge M. J., Irvine R. F. Inositol phosphates and cell signalling. Nature. 1989 Sep 21;341(6239):197–205. doi: 10.1038/341197a0. [DOI] [PubMed] [Google Scholar]
  4. Bird G. S., Takemura H., Thastrup O., Putney J. W., Jr, Menniti F. S. Mechanisms of activated Ca2+ entry in the rat pancreatoma cell line, AR4-2J. Cell Calcium. 1992 Jan;13(1):49–58. doi: 10.1016/0143-4160(92)90029-r. [DOI] [PubMed] [Google Scholar]
  5. Chow S. C., Jondal M. Ca2+ entry in T cells is activated by emptying the inositol 1,4,5-triphosphate sensitive Ca2+ pool. Cell Calcium. 1990 Nov-Dec;11(10):641–646. doi: 10.1016/0143-4160(90)90018-p. [DOI] [PubMed] [Google Scholar]
  6. Chow S. C., Jondal M. Polyunsaturated free fatty acids stimulate an increase in cytosolic Ca2+ by mobilizing the inositol 1,4,5-trisphosphate-sensitive Ca2+ pool in T cells through a mechanism independent of phosphoinositide turnover. J Biol Chem. 1990 Jan 15;265(2):902–907. [PubMed] [Google Scholar]
  7. Clementi E., Scheer H., Zacchetti D., Fasolato C., Pozzan T., Meldolesi J. Receptor-activated Ca2+ influx. Two independently regulated mechanisms of influx stimulation coexist in neurosecretory PC12 cells. J Biol Chem. 1992 Feb 5;267(4):2164–2172. [PubMed] [Google Scholar]
  8. Cui Z. J., Dannies P. S. Thyrotropin-releasing hormone-mediated Mn2+ entry in perifused rat anterior pituitary cells. Biochem J. 1992 Apr 15;283(Pt 2):507–513. doi: 10.1042/bj2830507. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Duddy S. K., Kass G. E., Orrenius S. Ca2(+)-mobilizing hormones stimulate Ca2+ efflux from hepatocytes. J Biol Chem. 1989 Dec 15;264(35):20863–20866. [PubMed] [Google Scholar]
  10. Gouy H., Cefai D., Christensen S. B., Debre P., Bismuth G. Cyclic AMP- and inositol phosphate-independent inhibition of Ca2+ influx by cholera toxin in CD3-stimulated Jurkat T cells. A study with a cholera toxin-resistant cell variant and the Ca2+ endoplasmic reticulum-ATPase inhibitor thapsigargin. J Immunol. 1991 Aug 1;147(3):757–766. [PubMed] [Google Scholar]
  11. Grynkiewicz G., Poenie M., Tsien R. Y. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem. 1985 Mar 25;260(6):3440–3450. [PubMed] [Google Scholar]
  12. Imboden J. B., Stobo J. D. Transmembrane signalling by the T cell antigen receptor. Perturbation of the T3-antigen receptor complex generates inositol phosphates and releases calcium ions from intracellular stores. J Exp Med. 1985 Mar 1;161(3):446–456. doi: 10.1084/jem.161.3.446. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Jackson T. R., Patterson S. I., Thastrup O., Hanley M. R. A novel tumour promoter, thapsigargin, transiently increases cytoplasmic free Ca2+ without generation of inositol phosphates in NG115-401L neuronal cells. Biochem J. 1988 Jul 1;253(1):81–86. doi: 10.1042/bj2530081. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kass G. E., Duddy S. K., Moore G. A., Orrenius S. 2,5-Di-(tert-butyl)-1,4-benzohydroquinone rapidly elevates cytosolic Ca2+ concentration by mobilizing the inositol 1,4,5-trisphosphate-sensitive Ca2+ pool. J Biol Chem. 1989 Sep 15;264(26):15192–15198. [PubMed] [Google Scholar]
  15. Khan A. A., Steiner J. P., Klein M. G., Schneider M. F., Snyder S. H. IP3 receptor: localization to plasma membrane of T cells and cocapping with the T cell receptor. Science. 1992 Aug 7;257(5071):815–818. doi: 10.1126/science.1323146. [DOI] [PubMed] [Google Scholar]
  16. Khan A. A., Steiner J. P., Snyder S. H. Plasma membrane inositol 1,4,5-trisphosphate receptor of lymphocytes: selective enrichment in sialic acid and unique binding specificity. Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):2849–2853. doi: 10.1073/pnas.89.7.2849. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kuno M., Gardner P. Ion channels activated by inositol 1,4,5-trisphosphate in plasma membrane of human T-lymphocytes. Nature. 1987 Mar 19;326(6110):301–304. doi: 10.1038/326301a0. [DOI] [PubMed] [Google Scholar]
  18. Llopis J., Chow S. B., Kass G. E., Gahm A., Orrenius S. Comparison between the effects of the microsomal Ca(2+)-translocase inhibitors thapsigargin and 2,5-di-(t-butyl)-1,4-benzohydroquinone on cellular calcium fluxes. Biochem J. 1991 Jul 15;277(Pt 2):553–556. doi: 10.1042/bj2770553. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Llopis J., Kass G. E., Gahm A., Orrenius S. Evidence for two pathways of receptor-mediated Ca2+ entry in hepatocytes. Biochem J. 1992 May 15;284(Pt 1):243–247. doi: 10.1042/bj2840243. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lückhoff A., Clapham D. E. Inositol 1,3,4,5-tetrakisphosphate activates an endothelial Ca(2+)-permeable channel. Nature. 1992 Jan 23;355(6358):356–358. doi: 10.1038/355356a0. [DOI] [PubMed] [Google Scholar]
  21. Mason M. J., Mahaut-Smith M. P., Grinstein S. The role of intracellular Ca2+ in the regulation of the plasma membrane Ca2+ permeability of unstimulated rat lymphocytes. J Biol Chem. 1991 Jun 15;266(17):10872–10879. [PubMed] [Google Scholar]
  22. Merritt J. E., Jacob R., Hallam T. J. Use of manganese to discriminate between calcium influx and mobilization from internal stores in stimulated human neutrophils. J Biol Chem. 1989 Jan 25;264(3):1522–1527. [PubMed] [Google Scholar]
  23. Moore G. A., McConkey D. J., Kass G. E., O'Brien P. J., Orrenius S. 2,5-Di(tert-butyl)-1,4-benzohydroquinone--a novel inhibitor of liver microsomal Ca2+ sequestration. FEBS Lett. 1987 Nov 30;224(2):331–336. doi: 10.1016/0014-5793(87)80479-9. [DOI] [PubMed] [Google Scholar]
  24. Morris A. P., Gallacher D. V., Irvine R. F., Petersen O. H. Synergism of inositol trisphosphate and tetrakisphosphate in activating Ca2+-dependent K+ channels. Nature. 1987 Dec 17;330(6149):653–655. doi: 10.1038/330653a0. [DOI] [PubMed] [Google Scholar]
  25. Nishizuka Y. The molecular heterogeneity of protein kinase C and its implications for cellular regulation. Nature. 1988 Aug 25;334(6184):661–665. doi: 10.1038/334661a0. [DOI] [PubMed] [Google Scholar]
  26. Pecht I., Corcia A., Liuzzi M. P., Alcover A., Reinherz E. L. Ion channels activated by specific Ti or T3 antibodies in plasma membranes of human T cells. EMBO J. 1987 Jul;6(7):1935–1939. doi: 10.1002/j.1460-2075.1987.tb02454.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Penner R., Matthews G., Neher E. Regulation of calcium influx by second messengers in rat mast cells. Nature. 1988 Aug 11;334(6182):499–504. doi: 10.1038/334499a0. [DOI] [PubMed] [Google Scholar]
  28. Putney J. W., Jr A model for receptor-regulated calcium entry. Cell Calcium. 1986 Feb;7(1):1–12. doi: 10.1016/0143-4160(86)90026-6. [DOI] [PubMed] [Google Scholar]
  29. Putney J. W., Jr Capacitative calcium entry revisited. Cell Calcium. 1990 Nov-Dec;11(10):611–624. doi: 10.1016/0143-4160(90)90016-n. [DOI] [PubMed] [Google Scholar]
  30. Stauderman K. A., Pruss R. M. Dissociation of Ca2+ entry and Ca2+ mobilization responses to angiotensin II in bovine adrenal chromaffin cells. J Biol Chem. 1989 Nov 5;264(31):18349–18355. [PubMed] [Google Scholar]
  31. Takemura H., Hughes A. R., Thastrup O., Putney J. W., Jr Activation of calcium entry by the tumor promoter thapsigargin in parotid acinar cells. Evidence that an intracellular calcium pool and not an inositol phosphate regulates calcium fluxes at the plasma membrane. J Biol Chem. 1989 Jul 25;264(21):12266–12271. [PubMed] [Google Scholar]
  32. Tepikin A. V., Voronina S. G., Gallacher D. V., Petersen O. H. Acetylcholine-evoked increase in the cytoplasmic Ca2+ concentration and Ca2+ extrusion measured simultaneously in single mouse pancreatic acinar cells. J Biol Chem. 1992 Feb 25;267(6):3569–3572. [PubMed] [Google Scholar]
  33. Thastrup O., Cullen P. J., Drøbak B. K., Hanley M. R., Dawson A. P. Thapsigargin, a tumor promoter, discharges intracellular Ca2+ stores by specific inhibition of the endoplasmic reticulum Ca2(+)-ATPase. Proc Natl Acad Sci U S A. 1990 Apr;87(7):2466–2470. doi: 10.1073/pnas.87.7.2466. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Thastrup O., Dawson A. P., Scharff O., Foder B., Cullen P. J., Drøbak B. K., Bjerrum P. J., Christensen S. B., Hanley M. R. Thapsigargin, a novel molecular probe for studying intracellular calcium release and storage. Agents Actions. 1989 Apr;27(1-2):17–23. doi: 10.1007/BF02222186. [DOI] [PubMed] [Google Scholar]
  35. Treves S., Di Virgilio F., Cerundolo V., Zanovello P., Collavo D., Pozzan T. Calcium and inositolphosphates in the activation of T cell-mediated cytotoxicity. J Exp Med. 1987 Jul 1;166(1):33–42. doi: 10.1084/jem.166.1.33. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Weiss A., Imboden J., Hardy K., Manger B., Terhorst C., Stobo J. The role of the T3/antigen receptor complex in T-cell activation. Annu Rev Immunol. 1986;4:593–619. doi: 10.1146/annurev.iy.04.040186.003113. [DOI] [PubMed] [Google Scholar]

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