Cyclosporin depolarizes human lymphocytes: earliest observed effect on cell metabolism

Sándor Damjanovich, Adorján Aszalós, Sally A. Mulhern, János Szöllösi, Margit Balázs, Lajos Trón, Mack J. Fulwyler

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Abstract

Cyclosporin A (CsA) produced dose‐dependent membrane depolarization of human peripheral blood lymphocytes. The phenomenon was investigated applying the membrane potential probe dihexyloxacarbocyanine iodide in a flow cytometer in combination with ionophores, hormones and monoclonal antibodies binding to different subclasses of lymphocytes and the anti‐interleukin 2 receptor antibody. Human interferon‐γ abolished the depolarizing effect of cyclosporin on lymphocytes. Interleukin 2 caused depolarization and also enhanced the effect of CsA. OKT4 and OKT8 monoclonal antibodies slightly hindered depolarization by CsA while OKT3, OKT11 and OKIa1 antibodies had no such effect. Valinomycin decreased CsA's effect on the membrane potential while the ionophore A‐23187 and ionomycin caused depolarizations that were additive with CsA's. CsA treatment released the isotope from 42K‐loaded human lymphocytes in a dose‐dependent fashion. CsA addition increased intracellular calcium content. CsA decreased the motional freedom of a spin probe in the membrane, but did not hinder the binding of fluoresceinated antibodies to the cell surface. These results suggest immediate alteration in membrane structure upon CsA treatment, causing potassium leakage and calcium ion uptake. These are the earliest detected effects of CsA on cells so far.

Original languageEnglish
Pages (from-to)763-768
Number of pages6
JournalEuropean journal of immunology
Volume17
Issue number6
DOIs
Publication statusPublished - 1987

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Damjanovich, S., Aszalós, A., Mulhern, S. A., Szöllösi, J., Balázs, M., Trón, L., & Fulwyler, M. J. (1987). Cyclosporin depolarizes human lymphocytes: earliest observed effect on cell metabolism. European journal of immunology, 17(6), 763-768. https://doi.org/10.1002/eji.1830170605