TY - JOUR
T1 - 1,25(OH)2D3 increases cytotoxicity and exocytosis in lymphokine-activated killer cells
AU - Ravid, Amiram
AU - Koren, Ruth
AU - Maron, Leah
AU - Liberman, Uri A.
N1 - Funding Information:
Thanks are due to Dr Z. Keinan for his help throughout this project. This research was supported by grant No. 85-00276 from the United States-Israel Binational Science foundation, Jerusalem, Israel, and by the Chuma Munka Averbuch Memorial Fund via the Israel Cancer Association. This work was presented in part at the ASBMR/IC-CRH first joint meeting 1989a nd at the eighth Vitamin D workshop 1991.
PY - 1993/10
Y1 - 1993/10
N2 - 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.
AB - 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.
KW - (Human) lymphocyte
KW - Calcium-ionophore
KW - Cytotoxicity
KW - Exocytosis
KW - Granzyme A
KW - Lymphokine-activated killer
UR - http://www.scopus.com/inward/record.url?scp=0027380716&partnerID=8YFLogxK
U2 - 10.1016/0303-7207(93)90103-Q
DO - 10.1016/0303-7207(93)90103-Q
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AN - SCOPUS:0027380716
SN - 0303-7207
VL - 96
SP - 133
EP - 139
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
IS - 1-2
ER -