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多环芳烃通过诱导骨髓前B淋巴细胞凋亡产生的免疫抑制作用。

Immunosuppressive effect of polycyclic aromatic hydrocarbons by induction of apoptosis of pre-B lymphocytes of bone marrow.

作者信息

Novosad Jakub, Fiala Zdenĕk, Borská Lenka, Krejsek Jan

机构信息

Charles University in Prague, Faculty of Medicine in Hradec Králové, Czech Republic.

出版信息

Acta Medica (Hradec Kralove). 2002;45(4):123-8.

Abstract

Polycyclic aromatic hydrocarbons (PAH) are ubiquitous environmental pollutants, distinguished by genotoxic, hepatotoxic, nephrotoxic and immunotoxic effects. Especially secondary toxicity after bioactivation by microsomal monooxygenases (dependent on cytochromes P450) is characteristic of them. The immunotoxic effect is the result of very global impact on immunological reactivity of an organism and immunosuppression by induction of apoptosis of pre-B lymphocytes represents one of its particular forms. It has been proved that the effect of PAH is caused mostly by the following mechanisms: enzymatic induction by the way of activation of AhR (Aromatic hydrocarbon Receptor); alteration of cellular DNA; development of oxidative stress; increase in the concentration of intercellular calcium and decline of activity of NF-kappaB (Nuclear Factor-kappa B). Most sensitive to these changes are particularly B-lymphocytic precursors and pre-B lymphocytes. Intensity of entire manifestations is also considerably dependent on the presence and intensity of mechanisms of active or passive resistance of cells.

摘要

多环芳烃(PAH)是普遍存在的环境污染物,具有遗传毒性、肝毒性、肾毒性和免疫毒性作用。特别是经微粒体单加氧酶(依赖细胞色素P450)生物活化后的二次毒性是其特征。免疫毒性作用是对机体免疫反应性产生非常全面影响的结果,通过诱导前B淋巴细胞凋亡导致的免疫抑制是其特殊形式之一。已证明PAH的作用主要由以下机制引起:通过激活芳烃受体(AhR)进行酶诱导;细胞DNA改变;氧化应激的发展;细胞内钙浓度增加以及核因子κB(NF-κB)活性下降。对这些变化最敏感的尤其是B淋巴细胞前体和前B淋巴细胞。整个表现的强度也在很大程度上取决于细胞主动或被动抵抗机制的存在和强度。

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