Document Detail


Organophosphorus pesticides induce apoptosis in human NK cells.
MedLine Citation:
PMID:  17681413     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Qing Li; Maiko Kobayashi; Tomoyuki Kawada
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-07-05
Journal Detail:
Title:  Toxicology     Volume:  239     ISSN:  0300-483X     ISO Abbreviation:  Toxicology     Publication Date:  2007 Sep 
Date Detail:
Created Date:  2007-08-27     Completed Date:  2007-10-16     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0361055     Medline TA:  Toxicology     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  89-95     Citation Subset:  IM    
Affiliation:
Department of Hygiene and Public Health, Nippon Medical School, 1-1-5 Sendagi, Tokyo, Japan. qing-li@nms.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / drug effects*
Caspase 3 / metabolism
Cell Line
Chlorpyrifos / toxicity*
Cysteine Proteinase Inhibitors / pharmacology
Dichlorvos / toxicity*
Dose-Response Relationship, Drug
Drug Antagonism
Humans
Insecticides / toxicity*
Killer Cells, Natural / drug effects*,  pathology
Oligopeptides / pharmacology
Time Factors
Chemical
Reg. No./Substance:
0/Cysteine Proteinase Inhibitors; 0/Insecticides; 0/Oligopeptides; 0/benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone; 2921-88-2/Chlorpyrifos; 62-73-7/Dichlorvos; EC 3.4.22.-/Caspase 3

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