Organophosphorus pesticides induce apoptosis in human NK cells.
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.
Department of Hygiene and Public Health, Nippon Medical School, 1-1-5 Sendagi, Tokyo, Japan. qing-li@nms.ac.jp
Qing
Q
Li
Maiko
M
Kobayashi
Tomoyuki
T
Kawada
D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D004390:Chlorpyrifos / Q000633:toxicity*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004006:Dichlorvos / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D006801:Humans; D007306:Insecticides / Q000633:toxicity*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000473:pathology; D009842:Oligopeptides / Q000494:pharmacology; D013997:Time Factors
D015853:Cysteine Proteinase Inhibitors; D007306:Insecticides; D009842:Oligopeptides; C110772:benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone; D004006:Dichlorvos; D053148:Caspase 3; D004390:Chlorpyrifos