Effect of ziram on natural killer, lymphokine-activated killer, and cytotoxic T lymphocyte activity.
Ziram is a carbamate pesticide, which is widely used throughout the world as a fungicide in agriculture and as an accelerating agent in latex production. In the present study, we investigated the effect of ziram at 0.031-4 μM in vitro on human natural killer (NK) and lymphokine-activated killer (LAK) and murine cytotoxic T lymphocyte (CTL) activity and found that it significantly inhibited all three activities in a concentration-dependent manner. To explore the mechanism of ziram-induced inhibition of NK activity, NK-92MI cells, a human NK cell line, were used. We previously confirmed that NK-92MI cells express CD56, perforin, granzyme (Gr) A, GrB, Gr3/K, and granulysin and are highly cytotoxic to K562 cells in the chromium release assay. NK-92MI cells were treated with ziram at 0.125-4 μM for 4 or 16 h at 37°C in vitro. Then, intracellular levels of perforin, GrA, GrB, Gr3/K, and granulysin were determined by flow cytometry. It was found that ziram significantly reduced Gr3/K, granulysin, perforin, GrA, and GrB levels. The extent of the decrease differed among the proteins, and the order was as follows: Gr3/K > granulysin > perforin, GrA, and GrB. Taken together, these findings suggest the ziram-induced inhibition of NK, LAK, and CTL activities to be at least partially mediated by decreases in the intracellular levels of Gr3/K, granulysin, perforin, GrA, and GrB.
Department of Hygiene and Public Health, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan. qing-li@nms.ac.jp
Qing
Q
Li
Maiko
M
Kobayashi
Tomoyuki
T
Kawada
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D002478:Cells, Cultured; D005659:Fungicides, Industrial / Q000633:toxicity*; D053804:Granzymes / Q000032:analysis; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects*; D007694:Killer Cells, Natural / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D054353:Perforin / Q000032:analysis; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects*; D015039:Ziram / Q000633:toxicity*
D000945:Antigens, Differentiation, T-Lymphocyte; D005659:Fungicides, Industrial; C075005:GNLY protein, human; D054353:Perforin; D015039:Ziram; D053804:Granzymes