Brief exposure to triphenyltin produces irreversible inhibition of the cytotoxic function of human natural killer cells.

Brief exposure to triphenyltin produces irreversible inhibition of the cytotoxic function of human natural killer cells.
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短暂接触三苯基锡会对人类自然杀伤细胞的细胞毒功能产生不可逆的抑制。

DOI:
10.1016/s0013-9351(03)00043-4
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发表时间:
2003
影响因子:
8.3
通讯作者:
Loganathan,BommannaG
Loganathan,BommannaG
中科院分区:
环境科学与生态学2区
文献类型:
--
作者:
Whalen,MargaretM;Wilson,Sharnise;Gleghorn,Carrnes;Loganathan,BommannaG

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苯基锡(PT)化合物(单苯基锡、二苯基锡和三苯基锡)用于农业和消费品。它们污染环境,并对包括人类在内的水生和陆生动物产生毒性影响。在早期的一项研究中,我们证明了PTs (1μM,体外暴露1小时)可以对人类自然杀伤(NK)细胞的肿瘤杀伤功能产生相当大的抑制作用(高达85%)。在这项研究中,我们检测了短暂暴露于PTs(1小时)后细胞毒性功能是否可以恢复。将新分离的淋巴细胞暴露于三苯基锡(TPT)或二苯基锡(DPT)中1h。然后去除化合物,细胞在无pt培养基中孵育长达6天。结果表明,暴露于750nM TPT下1h可导致nk细胞毒功能下降~ 63±10%。然而,如果细胞暴露在750nM TPT中1小时,然后在无TPT的培养基中孵育24小时,细胞毒性功能损失91±12%。nk细胞毒功能在去除TPT后的6天内仍然受到抑制。暴露于高达5μM DPT 1小时后立即检测细胞nk -细胞毒性功能,但未造成细胞毒性功能的丧失。然而,如果细胞在5μM DPT中暴露1小时后,在无DPT培养基中孵育24小时,细胞毒性被抑制68±29%,并且这种抑制持续至少6天。这些结果表明,短期暴露于PTs会对人类nk细胞功能产生持续的负面影响。将PTs与丁胺素(BTs)的持续效应进行了比较。
Phenyltin (PT) compounds (mono-, di-, and triphenyltins) are used in agricultural and consumer products. They contaminate the environment and have toxic effects on aquatic and terrestrial animals including humans. In an earlier study we demonstrated that PTs (1μM, for 1h in vitro exposure) could cause considerable inhibition of the tumor-killing function of human natural killer (NK) cells (as much as 85%). In this study we examined whether cytotoxic function can be recovered after a brief exposure (1h) to PTs. Freshly isolated lymphocytes were exposed to triphenyltin (TPT) or diphenyltin (DPT) for 1h. The compound was then removed and the cells were incubated in PT-free medium for as long as 6 days. The results indicated that exposure to 750nM TPT for 1h caused an ∼63±10% decrease in NK-cytotoxic function. However, if the cells were exposed to 750nM TPT for 1h and then allowed to incubate in TPT-free medium for 24h, there was a 91±12% loss of cytotoxic function. NK-cytotoxic function remained inhibited for as long as 6 days after removal of the TPT. A 1-h exposure to as much as 5μM DPT caused no loss of NK-cytotoxic function when the cells were tested immediately after the exposure. However, if the cells were allowed to incubate in DPT-free medium for 24h after the 1-h exposure to 5μM DPT, cytotoxicity was inhibited by 68±29% and this inhibition persisted for at least 6 days. These results indicated that short-term exposure to PTs caused persistent negative effects on human NK-cell function. The persistent effects of PTs are compared to those of the butyltins (BTs).