Inhibition of interleukin 2 driven proliferation of mouse CTLL2 cells, by selected carbamate and organophosphate insecticides and congeners of carbaryl.
Inhibition of interleukin 2 driven proliferation of mouse CTLL2 cells, by selected carbamate and organophosphate insecticides and congeners of carbaryl.
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DOI：
10.3109/08923979309025994
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发表时间：
1993
影响因子：
3.3
通讯作者：
G. Casale;J. Vennerstrom;S. Bavari;Tian Lan Wang
中科院分区：
文献类型：
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作者：
G. Casale;J. Vennerstrom;S. Bavari;Tian Lan Wang
抗胆碱酯酶（antiCHE）杀虫剂是世界上广泛使用的一大类杀虫剂，其通过使催化位点处的丝氨酸残基氨甲酰化或磷酸化来抑制丝氨酸水解酶。这些杀虫剂被认为是丝氨酸水解酶依赖性免疫功能的潜在抑制剂，包括白细胞介素2（IL 2）信号传导。我们实验室先前的研究已经证明西维因（一种抗CHE杀虫剂）对IL 2驱动的1）小鼠CTLL 2细胞的增殖、2）人自然杀伤（NK）细胞的增殖和3）人NK细胞对靶细胞杀伤的增强产生显著的浓度依赖性抑制。在本研究中，我们研究了8种抗CHE杀虫剂（4种氨基甲酸酯和4种有机磷酸酯）抑制小鼠CTLL 2细胞IL 2依赖性增殖的潜力。对T细胞的抑制作用大小顺序为西维因=敌敌畏>甲硫威>克百威>对氧磷>速灭磷>涕灭威=久效磷。鉴于西维因（一种具有低胆碱能毒性的氨基甲酸酯）的相对高的抑制效力，测试了西维因的3种代谢物和5种同系物抑制CTLL 2增殖的效力。数据表明1-萘酚离去基团对西维因抑制T细胞增殖的显著贡献，并且与丝氨酸水解酶的抑制作为有助于观察到的IL 2依赖性增殖抑制的机制一致。
The anticholinesterase (antiCHE) insecticides, a large family of pesticides used extensively throughout the world, inhibit serine hydrolases by carbamylating or phosphorylating a serine residue at the catalytic site. These insecticides are viewed as potential inhibitors of serine hydrolase-dependent immune functions including interleukin 2 (IL2) signalling. Previous studies in our laboratory have demonstrated that carbaryl (an antiCHE insecticide) produces a marked concentration-dependent inhibition of IL2 driven 1) proliferation of mouse CTLL2 cells, 2) proliferation of human natural killer (NK) cells, and 3) enhancement of target cell killing by human NK cells. In the present study, we examined the potential of 8 antiCHE insecticides (4 carbamates and 4 organophosphates) to inhibit IL2-dependent proliferation of mouse CTLL2 cells. The order of potency for T cell inhibition was carbaryl = dichlorvos > methiocarb > carbofuran > paraoxon > mevinphos > aldicarb = monocrotophos. In view of the relatively high inhibitory potency of carbaryl (a carbamate with low cholinergic toxicity), 3 metabolites and 5 congeners of carbaryl were tested for potency to inhibit CTLL2 proliferation. The data indicate a significant contribution of the 1-naphthol leaving group to inhibition of T cell proliferation by carbaryl, and are consistent with inhibition of a serine hydrolase(s) as a mechanism contributing to the observed inhibition of IL2-dependent proliferation.