1,25(OH)2D3 increases cytotoxicity and exocytosis in lymphokine-activated killer cells

Amiram Ravid*, Ruth Koren, Leah Maron, Uri A. Liberman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

The effect of 1,25-dihydroxyvitamin D3 on lymphokine-activated killer (LAK) cells activity was studied. Treatment of LAK cells with 1,25-dihydroxyvitamin D3 for 24 h increased their cytotoxic activity without affecting cell proliferation. This effect was dose-dependent, detectable already at 10-11 M attaining 44 ± 7% increase at 10-8 M. 1,25-dihydroxyvitamin D3 increased LAK cell content of the cytotoxic granule granzyme A by 21%. Secretion of granzyme A by LAK cells was triggered by 12-O-tetradecanoylphorbol 13-acetate and the calcium ionophore A23187. 1,25-dihydroxyvitamin D3 decreased the lag preceding secretion, increased the rate constant of exocytosis and the fraction of granzyme A cell content secreted. The potentiation of exocytosis was more pronounced at suboptimal calcium ionophore concentration suggesting that 1,25-dihydroxyvitamin D3 affects a calcium-dependent process. Since exocytosis of cytotoxic granules is a pivotal event in the killing of tumor cells by LAK cells, it is plausible that the enhancement of this process underlies the stimulation of LAK cell cytotoxic activity by 1,25-dihydroxyvitamin D3.

Original languageEnglish
Pages (from-to)133-139
Number of pages7
JournalMolecular and Cellular Endocrinology
Volume96
Issue number1-2
DOIs
StatePublished - Oct 1993

Funding

FundersFunder number
Chuma Munka Averbuch Memorial Fund
United States-Israel Binational Science Foundation
Israel Cancer Association

    Keywords

    • (Human) lymphocyte
    • Calcium-ionophore
    • Cytotoxicity
    • Exocytosis
    • Granzyme A
    • Lymphokine-activated killer

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