| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2597331 | Toxicology | 2008 | 9 Pages |
Natural killer (NK), lymphokine-activated killer (LAK), and cytotoxic T lymphocyte (CTL) cells kill target cells by the directed release of cytolytic granules that contain perforin, granzymes, and granulysin. We have found previously that dimethyl 2,2-dichlorovinyl phosphate (DDVP, dichlorvos), an organophosphorus pesticide, significantly decreased the expression of perforin, granzyme A (GrA), and granulysin and inhibited NK, LAK, and CTL activities. To further explore the mechanism of organophosphorus pesticide-induced inhibition of cell-mediated cytolysis, we examined whether organophosphorus pesticides affect the expression of GrB and Gr3/K in NK cells. We used an interleukin-2 (IL-2) independent human NK cell line, NK-92CI. We confirmed that NK-92CI cells express intracellular GrB and Gr3/K by flow cytometry, that NK-92CI cells are highly cytotoxic to K562 cells with a chromium release assay, and that DDVP significantly inhibited cytolytic activity of NK-92CI cells in a dose- and time-dependent manner. We found that DDVP significantly decreased the expression of GrB and Gr3/K in NK-92CI cells in a dose- and time-dependent manner by flow cytometry. Immunocytochemical results showed that DDVP significantly decreases the level of GrB positive granules in NK-92CI cells, which may be due to degranulation. Taken together, DDVP significantly inhibits NK activity and reduces the intracellular GrB and Gr3/K levels in NK cells.
