Effect of carbamate pesticides on perforin, granzymes A-B-3/K, and granulysin in human natural killer cells.
We previously found that ziram, a carbamate pesticide, significantly reduced perforin, granzyme A (GrA), granzyme B (GrB), granzyme 3/K (Gr3/K), and granulysin (GRN) levels in NK-92MI cells, a human natural killer (NK) cell line. To investigate whether other carbamate pesticides also show similar toxicity on human NK cells, we conducted further experiments with NK-92CI cells, a human NK cell line, using a more sensitive assay. We previously confirmed that NK-92CI cells express CD56, perforin, GrA, GrB, Gr3/K, and GRN and are highly cytotoxic to K562 cells in a chromium release assay, which are more sensitive to organophosphorus pesticides and ziram than the NK-92MI cell line. NK-92CI cells were treated with ziram, thiram, maneb, or carbaryl at various concentrations for 4-24 h at 37°C in vitro. Thereafter, intracellular levels of perforin, GrA, GrB, Gr3/K, and GRN were determined by flow cytometry. It was found that all carbamate pesticides significantly reduced the intracellular levels of perforin, GrA, GrB, Gr3/K, and GRN in NK-92CI cells in a dose-dependent manner. However, the strength of the effect differed among the pesticides, and the order was thiram > ziram > maneb > carbaryl. In addition, it was also found that the degree of the reductions differed among the five proteins, with perforin more sensitive to pesticides than GRN, GrA, GrB, and Gr3/K, and the order was perforin > GRN > Gr3/K ≒ GrA ≒ GrB.
Department of Hygiene and Public Health, Nippon Medical School, Tokyo, Japan qing-li@nms.ac.jp.
Qing
Q
Li
Department of Hygiene and Public Health, Nippon Medical School, Tokyo, Japan.
Maiko
M
Kobayashi
Department of Hygiene and Public Health, Nippon Medical School, Tokyo, Japan.
Tomoyuki
T
Kawada
D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism*; D002219:Carbamates / Q000494:pharmacology*; D002460:Cell Line; D053804:Granzymes / Q000378:metabolism*; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000378:metabolism; D054353:Perforin / Q000378:metabolism*; D010575:Pesticides / Q000494:pharmacology*; D015039:Ziram / Q000494:pharmacology
D000945:Antigens, Differentiation, T-Lymphocyte; D002219:Carbamates; C075005:GNLY protein, human; D010575:Pesticides; D054353:Perforin; D015039:Ziram; C509213:GZMB protein, human; C088546:GZMK protein, human; D053804:Granzymes; C509212:GZMA protein, human
NK cells; carbaryl; granulysin; granzyme; maneb; perforin; thiram