Effect of thapsigargin on cytoplasmic Ca2+ and proliferation of human lymphocytes in relation to AIDS

O Scharff, B Foder, Ole Thastrup, B Hofmann, J Møller, L P Ryder, K D Jacobsen, E Langhoff, E Dickmeiss, S B Christensen

    45 Citations (Scopus)

    Abstract

    The tumor-promoting sesquiterpene lactone, thapsigargin, induced a dose-dependent increase of the cytoplasmic Ca2+ concentration ([ Ca2+]i) in human lymphocytes from a resting level between 100 and 150 nM up to about 1 microM. Half-maximum response was found at about 1 nM of thapsigargin, full response at 100 nM. The effect of thapsigargin on [Ca2+]i exceeded that of phytohaemagglutinin (PHA) which raised [Ca2+]i to maximum 300 nM. In combination with phorbol 12-myristate 13-acetate (PMA), thapsigargin stimulated the proliferation of normal lymphocytes to the same extent as did PHA, whereas the thapsigargin/PMA treatment could not restore the defective proliferation of AIDS lymphocytes in spite of the increased [Ca2+]i. Thapsigargin or PMA added separately had no stimulatory effects on cell proliferation. The thapsigargin/PMA treatment caused an increase in the interleukin-2 (IL-2) production of the lymphocytes, which was much higher than that caused by the PHA treatment, even in AIDS lymphocytes. Moreover, the thapsigargin/PMA treatment stimulated the expression of the IL-2 receptors on both normal and AIDS lymphocytes, similar to the effect of PHA. It is concluded that thapsigargin exerts its effects on lymphocyte proliferation by increasing [Ca2+]i, and that the general defect of AIDS lymphocytes, rather than being ascribed to the initiating signal systems, is associated with later events related to DNA synthesis and proliferation.
    Original languageEnglish
    JournalBBA General Subjects
    Volume972
    Issue number3
    Pages (from-to)257-64
    Number of pages8
    ISSN0304-4165
    Publication statusPublished - 1988

    Keywords

    • Acquired Immunodeficiency Syndrome
    • Benzofurans
    • Calcimycin
    • Calcium
    • Cell Division
    • Cytoplasm
    • Drug Interactions
    • Fluorescent Dyes
    • Fura-2
    • Humans
    • Interleukin-2
    • Lymphocytes
    • Phytohemagglutinins
    • Plant Extracts
    • Receptors, Interleukin-2
    • Spectrometry, Fluorescence
    • Tetradecanoylphorbol Acetate
    • Thapsigargin

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