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Colchicine-sensitive structures and lymphocyte activation

W C Greene, C M Parker, C W Parker

    Journal of Immunology (Baltimore, Md. : 1950)
    |September 1, 1976
    PubMed
    Summary
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    Colchicine and vinblastine inhibit lymphocyte activation by lectins, affecting early nutrient uptake and DNA synthesis. These microtubule-disrupting drugs also alter cyclic AMP responses, suggesting a role in lymphocyte activation pathways.

    Area of Science:

    • Immunology
    • Cell Biology

    Background:

    • Lymphocyte activation by mitogenic lectins is crucial for immune responses.
    • Microtubules play roles in cellular processes, but their specific involvement in lymphocyte activation is not fully understood.

    Purpose of the Study:

    • To investigate the modulatory role of microtubules in human lymphocyte response to mitogenic lectins.
    • To determine the effects of colchicine and vinblastine on lectin-induced lymphocyte activation.

    Main Methods:

    • Human lymphocytes were stimulated with phytohemagglutinin and concanavalin A.
    • The uptake of [14C]-aminoisobutyric acid, [3H]-thymidine, and 45Ca was measured.
    • Cyclic AMP levels and 125I-concanavalin A binding were assessed.
    • Effects of colchicine, vinblastine, and lumicolchicine were evaluated.

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    Main Results:

    • Colchicine and vinblastine inhibited early amino acid and late thymidine uptake in stimulated lymphocytes.
    • These agents accentuated and prolonged the early cyclic AMP response to lectins.
    • Lumicolchicine, an inactive colchicine congener, had no effect.
    • 45Ca uptake and 125I-concanavalin A binding remained unaltered.

    Conclusions:

    • Microtubules or related structures modulate human lymphocyte activation by mitogenic lectins.
    • Inhibition of DNA synthesis and altered nutrient uptake suggest interference with early activation events.
    • The prolonged cyclic AMP response may be involved in the inhibitory mechanism, potentially via effects on membrane architecture and signal propagation.