1,25(OH)2D3 increases cytotoxicity and exocytosis in lymphokine-activated killer cells.
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.
Ravid
A
A
Basil and Gerald Felsenstein Medical Research Center (FMRC), Petah Tikva, Israel.
Koren
R
R
Maron
L
L
Liberman
U A
UA
D000704:Analysis of Variance; D000001:Calcimycin / Q000494:pharmacology; D002117:Calcitriol / Q000494:pharmacology*; D002455:Cell Division; D002460:Cell Line; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005089:Exocytosis / Q000187:drug effects; D006801:Humans; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects* / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000001:Calcimycin; D002117:Calcitriol; D013755:Tetradecanoylphorbol Acetate