Effect of carbamate pesticides on perforin, granzymes A-B-3/K, and granulysin in human natural killer cells

Int J Immunopathol Pharmacol. 2015 Sep;28(3):403-10. doi: 10.1177/0394632015582334. Epub 2015 Apr 28.

Abstract

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.

Keywords: NK cells; carbaryl; granulysin; granzyme; maneb; perforin; thiram.

MeSH terms

  • Antigens, Differentiation, T-Lymphocyte / metabolism*
  • Carbamates / pharmacology*
  • Cell Line
  • Granzymes / metabolism*
  • Humans
  • Killer Cells, Natural / drug effects*
  • Killer Cells, Natural / metabolism
  • Perforin / metabolism*
  • Pesticides / pharmacology*
  • Ziram / pharmacology

Substances

  • Antigens, Differentiation, T-Lymphocyte
  • Carbamates
  • GNLY protein, human
  • Pesticides
  • Perforin
  • Ziram
  • GZMB protein, human
  • GZMK protein, human
  • Granzymes
  • GZMA protein, human