Djokic Jelena, Popov Aleksandrov Aleksandra, Ninkov Marina, Mirkov Ivana, Zolotarevski Lidija, Kataranovski Dragan, Kataranovski Milena
Department of Ecology, Institute for Biological Research 'Sinisa Stankovic' .
J Immunotoxicol. 2015 Apr-Jun;12(2):115-23. doi: 10.3109/1547691X.2014.904955. Epub 2014 May 14.
Although numerous investigations have demonstrated a direct effect of cadmium (Cd) on peripheral blood mononuclear cell (PBMC) activity in humans, there is virtually no data concerning the in vivo impact of this metal on circulatory mononuclear cells. In this study, the effects of a sub-lethal Cd (1 mg/kg) dose were examined in rats 48 h following a single intraperitoneal injection. Cd treatment resulted in increased total peripheral blood leukocyte levels; however, decreases in PBMC numbers were seen. These changes coincided with an accumulation of mononuclear cells in the lungs and an increase in mononuclear cells expressing CD11b. A lack of effect of Cd on spontaneous nitric oxide (NO) production and on iNOS mRNA levels in the PBMC was also noted. Differential effects of Cd on PBMC inflammatory cytokine (IL-1β, TNFα, IL-6, IFNγ, and IL-17) gene expression and production were also seen. Specifically, except for IL-1β (levels increased), there were decreases (relative to controls) in mRNA levels for all the other cytokines examined. While there were no Cd treatment-related changes in spontaneous production of the cytokines assessed, there seemed to be a trend (p = 0.06) toward a decrease in spontaneous IL-6 release. When these harvested cells were stimulated ex vivo, there was no effect from Cd exposure on LPS-stimulated IL-1β and TNFα or on ConA-stimulated IFNγ or IL-17 production, but a decrease in IL-6 production in response to LPS was, again, noted. A preliminary study with a lower Cd dose (0.5 mg/kg) revealed some of the same outcomes noted here (mononuclear cell infiltration into lungs, increases in PBMC IL-1β mRNA levels), but differential (increased IL-17 mRNA levels) or newly detected outcomes (increased levels of IL-1α mRNA) as well. The described effects of the single in vivo exposure to Cd on PBMC might contribute to a better overall understanding of the immunomodulatory potential of this environmental contaminant.
尽管大量研究已证明镉（Cd）对人体外周血单个核细胞（PBMC）活性有直接影响，但实际上关于这种金属对循环单核细胞的体内影响的数据几乎没有。在本研究中，在大鼠单次腹腔注射48小时后，检测了亚致死剂量的镉（1毫克/千克）的影响。镉处理导致外周血白细胞总数增加；然而，PBMC数量减少。这些变化与肺中单核细胞的积聚以及表达CD11b的单核细胞增加同时出现。还注意到镉对PBMC中自发一氧化氮（NO）产生和诱导型一氧化氮合酶（iNOS）mRNA水平没有影响。镉对PBMC炎性细胞因子（IL-1β、TNFα、IL-6、IFNγ和IL-17）基因表达和产生也有不同影响。具体而言，除IL-1β（水平升高）外，所有其他检测细胞因子的mRNA水平均相对于对照组降低。虽然所评估的细胞因子的自发产生没有与镉处理相关的变化，但自发IL-6释放似乎有下降趋势（p = 0.06）。当这些收获的细胞在体外受到刺激时，镉暴露对脂多糖（LPS）刺激的IL-1β和TNFα或对刀豆蛋白A（ConA）刺激的IFNγ或IL-17产生没有影响，但再次注意到对LPS反应的IL-6产生减少。一项使用较低镉剂量（0.5毫克/千克）的初步研究揭示了此处提到的一些相同结果（单核细胞浸润到肺中，PBMC中IL-1β mRNA水平增加），但也有不同结果（IL-17 mRNA水平增加）或新检测到的结果（IL-1α mRNA水平增加）。所描述的单次体内暴露于镉对PBMC的影响可能有助于更好地全面了解这种环境污染物的免疫调节潜力。
