Advertisement

Pflügers Archiv - European Journal of Physiology

, Volume 463, Issue 2, pp 309–318 | Cite as

Differential pathways for calcium influx activated by concanavalin A and CD3 stimulation in Jurkat T cells

  • Bo Pang
  • Dong Hoon Shin
  • Kyung Sun Park
  • Yun Jeong Huh
  • Joohan Woo
  • Yin-Hua Zhang
  • Tong Mook KangEmail author
  • Ki-Young Lee
  • Sung Joon KimEmail author
Ion Channels, Receptors and Transporters

Abstract

Sustained increase in [Ca2+]c (Δ[Ca2+]c) is a critical early signal from T-cell receptor (TCR/CD3). In general, Ca2+-release activated Ca2+ channels (CRAC) are responsible for the Ca2+ influx and Δ[Ca2+]c after TCR/CD3 stimulation. However, T cells also express Ca2+-permeable nonselective cation channels such as TRPM2 and TRPC. Gd3+ is a relatively selective blocker for CRAC at micromolar concentrations. Here, Jurkat T cells were used to investigate the Gd3+-resistant Ca2+ influx (Δ[Ca2+]c,Gd) induced by concanavalin A (ConA, 1 μg/ml), a widely used mitogenic agent for T cells, or by anti-CD3 Ab (αCD3). αCD3-induced Δ[Ca2+]c was partly (~60%) inhibited by 1 μM Gd3+ while thapsigargin-induced Δ[Ca2+] was almost completely abolished. ConA-induced Δ[Ca2+] was mostly inhibited by 1 μM Gd3+ during the early phase (<30 s of ConA application) and became resistant during the late phase (>2 min). Induction of Δ[Ca2+]c,Gd by αCD3 and ConA was inhibited by 2-aminoethoxydiphenyl borate (2-APB) and by N-(p-amylcinnamoyl) anthranilic acid, indicating that TRPM2 and TRPC are involved in this process. Treatment with Pyr-3, a TRPC3-specific inhibitor, potently suppressed Δ[Ca2+]c,Gd by αCD3 (IC50, 0.16 μM). Patch clamp experiments demonstrated that the TRPM2 channels were activated by ConA, and the TRPC-like channels were activated by αCD3. Our present study suggests that TRPM2 and TRPC3 are activated by ConA and TCR/CD3, respectively, in Jurkat T cells and are responsible for the induction of Δ[Ca2+]c,Gd.

Keywords

Ca2+ influx Calcium signaling Lymphocyte Nonselective cation channel TRP channels 

Notes

Acknowledgment

This work was supported by a Korea Research Foundation Grant funded by the Korean Government (KRF-2008-314-E00008).

References

  1. 1.
    Amina S, Hashii M, Ma WJ, Yokoyama S, Lopatina O, Liu HX, Islam MS, Higashida H (2010) Intracellular calcium elevation induced by extracellular application of cyclic-ADP-ribose or oxytocin is temperature-sensitive in rodent NG108-15 neuronal cells with or without exogenous expression of human oxytocin receptors. J Neuroendocrinol 22:460–466PubMedCrossRefGoogle Scholar
  2. 2.
    Baba Y, Kurosaki T (2009) Physiological function and molecular basis of STIM1-mediated calcium entry in immune cells. Immunol Rev 231:174–188PubMedCrossRefGoogle Scholar
  3. 3.
    Beck A, Kolisek M, Bagley LA, Fleig A, Penner R (2006) Nicotinic acid adenine dinucleotide phosphate and cyclic ADP-ribose regulate TRPM2 channels in T lymphocytes. FASEB J 20:962–964PubMedCrossRefGoogle Scholar
  4. 4.
    Cahalan MD, Chandy KG (2009) The functional network of ion channels in T lymphocytes. Immunol Rev 231:59–87PubMedCrossRefGoogle Scholar
  5. 5.
    Cui J, Bian JS, Kagan A, McDonald TV (2002) CaT1 contributes to the stores-operated calcium current in Jurkat T-lymphocytes. J Biol Chem 277:47175–47183PubMedCrossRefGoogle Scholar
  6. 6.
    DeHaven WI, Jones BF, Petranka JG, Smyth JT, Tomita T, Bird GS, Putney JW Jr (2009) TRPC channels function independently of STIM1 and Orai1. J Physiol 587:2275–2298PubMedCrossRefGoogle Scholar
  7. 7.
    El Bawab S, Macovschi O, Thevenon C, Goncalves A, Nemoz G, Lagarde M, Prigent A-F (1996) Contribution of phosphoinositides and phosphatidylcholines to the production of phosphatidic acid upon concanavalin A stimulation of rat thymocytes. J Lipid Res 37:2098–2108PubMedGoogle Scholar
  8. 8.
    Feske S (2007) Calcium signalling in lymphocyte activation and disease. Nat Rev Immunol 7:690–702PubMedCrossRefGoogle Scholar
  9. 9.
    Gallo EM, Canté-Barrett K, Crabtree GR (2006) Lymphocyte calcium signaling from membrane to nucleus. Nat Immunol 7:25–32PubMedCrossRefGoogle Scholar
  10. 10.
    Gamberucci A, Giurisato E, Pizzo P, Tassi M, Giunti R, McIntosh DP, Benedetti A (2002) Diacylglycerol activates the influx of extracellular cations in T-lymphocytes independently of intracellular calcium-store depletion and possibly involving endogenous TRP6 gene products. Biochem J 364:245–254PubMedGoogle Scholar
  11. 11.
    Gasser A, Glassmeier G, Fliegert R, Langhorst MF, Meinke S, Hein D, Kruger S, Weber K, Heiner I, Oppenheimer N, Schwarz JR, Guse AH (2006) Activation of T cell calcium influx by the second messenger ADP-ribose. J Biol Chem 281:2489–2496PubMedCrossRefGoogle Scholar
  12. 12.
    Hong CW, Kim TK, Ham HY, Nam JS, Kim YH, Zheng H, Pang B, Min TK, Jung JS, Lee SN, Cho HJ, Kim EJ, Hong IH, Kang TC, Lee J, Oh SB, Jung SJ, Kim SJ, Song DK (2010) Lysophosphatidylcholine increases neutrophil bactericidal activity by enhancement of azurophil granule–phagosome fusion via glycine.GlyR alpha 2/TRPM2/p38 MAPK signaling. J Immunol 184:4401–4413PubMedCrossRefGoogle Scholar
  13. 13.
    Inada H, Iida T, Tominaga M (2006) Different expression patterns of TRP genes in murine B and T lymphocytes. Biochem Biophys Res Commun 350:762–767PubMedCrossRefGoogle Scholar
  14. 14.
    Kay JE (1991) Mechanisms of T lymphocyte activation. Immunol Lett 29:51–54PubMedCrossRefGoogle Scholar
  15. 15.
    Kiyonaka S, Kato K, Nishida M, Mio K, Numaga T, Sawaguchi Y, Yoshida T, Wakamori M, Mori E, Numata T, Ishii M, Takemoto H, Ojida A, Watanabe K, Uemura A, Kurose H, Morii T, Kobayashi T, Sato Y, Sato C, Hamachi I, Mori Y (2009) Selective and direct inhibition of TRPC3 channels underlies biological activities of a pyrazole compound. Proc Natl Acad Sci USA 106:5400–5405PubMedCrossRefGoogle Scholar
  16. 16.
    Kraft R, Grimm C, Frenzel H, Harteneck C (2006) Inhibition of TRPM2 cation channels by N-(p-amylcinnamoyl)anthranilic acid. Br J Pharmacol 148:264–273PubMedCrossRefGoogle Scholar
  17. 17.
    Lai ZF, Chen YZ, Nishi K (2003) Modulation of intracellular Cl homeostasis by lectin-stimulation in Jurkat T lymphocytes. Eur J Pharmacol 482:1–8PubMedCrossRefGoogle Scholar
  18. 18.
    Lee KP, Yuan JP, Hong JH, So I, Worley PF, Muallem S (2010) An endoplasmic reticulum/plasma membrane junction: STIM1/Orai1/TRPCs. FEBS Lett 584:2022–2202PubMedCrossRefGoogle Scholar
  19. 19.
    Lei HY, Chang CP (2009) Lectin of Concanavalin A as an anti-hepatoma therapeutic agent. J Biomed Sci 16:10PubMedCrossRefGoogle Scholar
  20. 20.
    Liao Y, Plummer NW, George MD, Abramowitz J, Zhu MX, Birnbaumer L (2009) A role for Orai in TRPC-mediated Ca2+ entry suggests that a TRPC: Orai complex may mediate store and receptor operated Ca2+ entry. Proc Natl Acad Sci USA 106:3202–3206PubMedCrossRefGoogle Scholar
  21. 21.
    Lichtman AH, Segel GB, Lichtman MA (1983) The role of calcium in lymphocyte proliferation. Blood 61:413–422PubMedGoogle Scholar
  22. 22.
    Nam JH, Shin DH, Zheng H, Kang JS, Kim WK, Kim SJ (2009) Inhibition of store-operated Ca2+ entry channels and K+ channels by caffeic acid phenethylester in T lymphocytes. Eur J Pharmacol 612:153–160PubMedCrossRefGoogle Scholar
  23. 23.
    Naziroğlu M (2007) New molecular mechanisms on the activation of TRPM2 channels by oxidative stress and ADP-ribose. Neurochem Res 32:1990–2001PubMedCrossRefGoogle Scholar
  24. 24.
    Oh-hora M, Rao A (2008) Calcium signaling in lymphocytes. Curr Opin Immunol 20:250–258PubMedCrossRefGoogle Scholar
  25. 25.
    Perraud AL, Fleig A, Dunn CA, Bagley LA, Launay P, Schmitz C, Stokes AJ, Zhu Q, Bessman MJ, Penner R, Kinet JP, Scharenberg AM (2001) ADP-ribose gating of the calcium-permeable LTRPC2 channel revealed by Nudix motif homology. Nature 411:595–599PubMedCrossRefGoogle Scholar
  26. 26.
    Philipp S, Strauss B, Hirnet D, Wissenbach U, Mery L, Flockerzi V, Hoth M (2003) TRPC3 mediates T-cell receptor-dependent calcium entry in human T-lymphocytes. J Biol Chem 278:26629–26638PubMedCrossRefGoogle Scholar
  27. 27.
    Rabinovich GA, Toscano MA (2009) Turning ‘sweet’ on immunity: galectin–glycan interactions in immune tolerance and inflammation. Nat Rev Immunol 9:338–352PubMedCrossRefGoogle Scholar
  28. 28.
    Sano Y, Inamura K, Miyake A, Mochizuki S, Yokoi H, Matsushime H, Furuichi K (2001) Immunocyte Ca2+ influx system mediated by LTRPC2. Science 293:1327–1330PubMedCrossRefGoogle Scholar
  29. 29.
    Shin DH, Seo EY, Pang B, Nam JH, Kim HS, Kim WK, Kim SJ (2011) Inhibition of Ca2+-release activated Ca2+ channel (CRAC) and K+ channels by curcumin in T lymphocytes. J Pharmacol Sci 115:144–154PubMedCrossRefGoogle Scholar
  30. 30.
    Togashi K, Inadal H, Tominaga M (2008) Inhibition of the transient receptor potential cation channel TRPM2 by 2-aminoethoxydiphenyl borate (2-APB). Br J Pharmacol 153:1324–1330PubMedCrossRefGoogle Scholar
  31. 31.
    Togashi T, Hara Y, Tominaga T, Higashi T, Konishi Y, Mori Y, Tominaga M (2006) TRPM2 activation by cyclic ADP-ribose at body temperature is involved in insulin secretion. EMBO J 25:1804–1815PubMedCrossRefGoogle Scholar
  32. 32.
    Walzel H, Blach M, Hirabayashi J, Kasai KI, Brock J (2000) Involvement of CD2 and CD3 in galectin-1 induced signaling in human Jurkat T-cells. Glycobiology 10:131–140PubMedCrossRefGoogle Scholar
  33. 33.
    Wehrhahn J, Kraft R, Harteneck C, Hauschildt S (2010) Transient receptor potential melastatin 2 is required for lipopolysaccharide-induced cytokine production in human monocytes. J Immunol 184:2386–2393PubMedCrossRefGoogle Scholar
  34. 34.
    Wenning AS, Neblung K, Strauss B, Wolfs MJ, Sappok A, Hoth M, Schwarz EC (2011) TRP expression pattern and the functional importance of TRPC3 in primary human T-cells. Biochim Biophys Acta 1813:412–423PubMedCrossRefGoogle Scholar
  35. 35.
    Yamamoto S, Shimizu S, Kiyonaka S, Takahashi N, Wajima T, Hara Y, Negoro T, Hiroi T, Kiuchi Y, Okada T, Kaneko S, Lange I, Fleig A, Penner R, Nishi M, Takeshima H, Mori Y (2008) TRPM2-mediated Ca2+ influx induces chemokine production in monocytes that aggravates inflammatory neutrophil infiltration. Nat Med 14:738–747PubMedCrossRefGoogle Scholar
  36. 36.
    Yuan JP, Kim MS, Zeng W, Shin DM, Huang G, Worley PF, Muallem S (2009) TRPC channels as STIM1-regulated SOCs. Channels 3:221–225PubMedCrossRefGoogle Scholar
  37. 37.
    Zweifach A, Lewis RS (1993) Mitogen-regulated Ca2+ current of T lymphocytes is activated by depletion of intracellular Ca2+ stores. Proc Natl Acad Sci USA 90:6295–6299PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Bo Pang
    • 1
    • 2
  • Dong Hoon Shin
    • 1
  • Kyung Sun Park
    • 3
  • Yun Jeong Huh
    • 1
  • Joohan Woo
    • 1
  • Yin-Hua Zhang
    • 1
  • Tong Mook Kang
    • 4
    Email author
  • Ki-Young Lee
    • 5
  • Sung Joon Kim
    • 1
    • 6
    Email author
  1. 1.Department of PhysiologySeoul National University College of MedicineSeoulRepublic of Korea
  2. 2.Key Laboratory of Hormones and Development, Ministry of Health Metabolic Diseases HospitalTianjin Medical UniversityTianjinChina
  3. 3.Division of Integrative Biosciences and BiotechnologyPohang University of Science and TechnologyPohangRepublic of Korea
  4. 4.Department of PhysiologySBRI, Sungkyunkwan University School of MedicineSuwonRepublic of Korea
  5. 5.Department of Molecular Cell BiologySBRI, Sungkyunkwan University School of MedicineSuwonRepublic of Korea
  6. 6.Ischemic/Hypoxic Disease InstituteSeoul National University College of MedicineSeoulRepublic of Korea

Personalised recommendations