Biopolym. Cell. 2000; 16(3):225-228.
Structure and Function of Biopolymers
Effects of interferon-α/β on Ca2+ in flux and binding in murine thymocytes
1Dolgaya E. V., 1Rozhmanova O. M., 1Stelmakh L. N., 1Miransky A. V., 2Kudryavets Yu. J.
  1. Bogomoletz Institute of Physiology, NAS of Ukraine
    4, Bogomolets Str., Kyiv, Ukraine, 01024
  2. R. E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine
    45, Vasilkivska Str., Kyiv, Ukraine, 01022


In order to determine the role of calcium in interferon (IFN)-induced immunomodulation, we investigated calcium transport and binding induced by murine IFN-α/β in murine thymocytes. By radiometric method, it was found that a rapid, more than 5-fold, increase in 45Ca2+ influx developed and reached a plateau within 10 min. At the same time the amount of 45Ca2+ associated with the cell surface half decreased. During next 30 min the recovery of 45Ca2+ binding to control level in INF-induced lymphocytes occured. 45Ca2+ influx in thymocytes was dose-dependent. The maximal increase in calcium influx was observed at the IFN concentration of 600 W/ml. Pretreatment of thymocytes with a calcium channel blacker, verapamil, at the doses about 30mkM for 20 min before IFN application significantly decreased 45Ca2+ influx. Depolarization of thymocytes up to 25 mM by increasing the extracellular K+ concentration resulted in complete inhibition of 45Ca2+ influx. Our data indicate that in murine thymocytes IFN-induced calcium influx occcured via voltage-operated calcium channels.


[1] Smorodintsev AA, Iovlev VI, Stepanov AN. Interferon. Itogi Nauki i Tekhniki (Virusologiia; Vol. 13). M.: VINITI, 1987 .
[2] Ashman RF. Lymphocyte activation, in Fundamental Immunology, Paul WE Ed Raven Pres New York 1984.
[3] De Maeyer-Guignard J, De Maeyer E. Immunomodulation by interferons: recent developments. Interferon. 1985;6:69-91.
[4] Singh VK, Maheshwari RK, Krisima G, Friedman RM. Effects of interferon on calcium. The 2-5 A molecular and clinical aspects of the interferon-regulated pathway. New York: Alan Liss. Inc., 1985: 351-6.
[5] Martino G, Brambilla E, Filippi M, Martinelli V, Colombo B, Rodegher M, Comi G, Grimaldi LM. Interferon-gamma activated calcium influx in peripheral blood lymphocytes from patients with primary and secondary progressive multiple sclerosis. J Neurol Neurosurg Psychiatry. 1996;61(5):515-7.
[6] Aas V, Larsen K, Iversen JG. IFN-gamma induces calcium transients and increases the capacitative calcium entry in human neutrophils. J Interferon Cytokine Res. 1998;18(3):197-205.
[7] Knight E Jr, Korant BD. A cell surface alteration in mouse L cells induced by interferon. Biochem Biophys Res Commun. 1977;74(2):707-13.
[8] B?yum A. Separation of leukocytes from blood and bone marrow. Introduction. Scand J Clin Lab Invest Suppl. 1968;97:7.
[9] Iwagaki H, Fuchimoto S, Miyake M, Aoki H, Orita K. Interferon-gamma activates the voltage-gated calcium channel in RPMI 4788 cells. Biochem Biophys Res Commun. 1988;153(3):1276-81.
[10] Klein JB, McLeish KR, Sonnenfeld G, Dean WL. Potential mechanisms of cytosolic calcium modulation in interferon-gamma treated U937 cells. Biochem Biophys Res Commun. 1987;145(3):1295-30.
[11] Hansen AB, Bouchelouche PN, Lillevang ST, Andersen CB. Interferon-gamma increases cellular calcium ion concentration and inositol 1,4,5-trisphosphate formation in human renal carcinoma cells: relation to ICAM-1 antigen expression. Br J Cancer. 1994;69(2):291-8.
[12] Kostyuk PG. Calcium and cellular excitability. M.: Nauka, 1986;5-26.
[13] Russell AJ, Fersht AR. Rational modification of enzyme catalysis by engineering surface charge. Nature. 1987 Aug 6-12;328(6130):496-500.