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Organophosphorus pesticides induce apoptosis in human NK cells
Qing Li1, Maiko Kobayashi, Tomoyuki Kawada
1Department of Hygiene and Public Health, Nippon Medical School, 1-1-5 Sendagi, Tokyo, Japan. qing-li@nms.ac.jp
Abstract:
We found previously that organophosphorus pesticides (OPs) significantly inhibited natural killer (NK) activity. To explore the mechanism of OP-induced inhibition of NK activity, we investigated whether OPs can induce apoptosis in NK cells in the present study. We used NK-92CI and NK-92MI cells, which are interleukin-2 independent human NK cell lines. NK-92CI and/or NK-92MI were treated with dichlorvos (DDVP) or chlorpyrifos (CP) at 0-100 ppm for 1-72 h at 37 degrees C in vitro. Apoptosis induced by DDVP and CP was determined by FITC-Annexin V staining and the intracellular level of active caspase-3 was analysed by flow cytometry. We found that DDVP and CP significantly induced apoptosis in NK-92CI and NK-92MI cells in a dose- and time-dependent manner. DDVP also induced an increase of intracellular active caspase-3 in NK-92CI in a dose- and time-dependent manner, and a caspase-3 inhibitor, Z-DEVD-FMK, significantly inhibited DDVP-induced apoptosis, suggesting that this apoptosis is partially mediated by activation of intracellular caspase-3. The pattern of apoptosis induced by CP differed from that induced by DDVP. CP showed a faster response than DDVP at higher doses; whereas, DDVP showed a slower, but stronger apoptosis-inducing ability than CP at lower doses. Moreover, the response to OPs differed between NK-92CI and NK-92MI cells, and NK-92CI was more sensitive to OPs than NK-92MI. This is similar to the inhibition of NK activity induced by DDVP, in which NK-92CI was more easily inhibited by DDVP than NK-92MI. Taken together, these findings suggest that OP-induced inhibition of NK activity may be at least partially mediated by OP-induced apoptosis in NK.
Insights
Organophosphorus pesticides (OPs) induce apoptosis, or programmed cell death, in natural killer (NK) cells. This finding suggests OPs may impair immune function by triggering NK cell death.
Area of Science:
- Immunotoxicology
- Cell Biology
- Pesticide Toxicology
Background:
- Organophosphorus pesticides (OPs) are known to inhibit natural killer (NK) cell activity.
- The precise mechanisms underlying OP-induced NK cell dysfunction require further elucidation.
Purpose of the Study:
- To investigate whether organophosphorus pesticides (OPs) induce apoptosis in human NK cell lines.
- To explore the role of caspase-3 activation in OP-induced NK cell apoptosis.
Main Methods:
- Human NK cell lines (NK-92CI and NK-92MI) were treated with dichlorvos (DDVP) or chlorpyrifos (CP) in vitro.
- Apoptosis was assessed using FITC-Annexin V staining.
- Intracellular active caspase-3 levels were analyzed by flow cytometry; caspase-3 inhibition was also tested.
Main Results:
- Both DDVP and CP significantly induced apoptosis in NK-92CI and NK-92MI cells in a dose- and time-dependent manner.
- DDVP treatment increased intracellular active caspase-3, and a caspase-3 inhibitor partially blocked DDVP-induced apoptosis.
- CP exhibited a faster but weaker apoptotic effect at high doses compared to DDVP, while DDVP showed a slower but stronger effect at low doses. NK-92CI cells were more sensitive to OPs than NK-92MI cells.
Conclusions:
- Organophosphorus pesticides (OPs) can induce apoptosis in human NK cells, at least partially through caspase-3 activation.
- OP-induced NK cell apoptosis may contribute to the observed inhibition of NK cell activity.
- Differential sensitivity of NK cell lines to OPs highlights the complexity of pesticide immunotoxicity.
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