Polycyclic aromatic hydrocarbons affect functional differentiation and maturation of human monocyte-derived dendritic cells
Polycyclic aromatic hydrocarbons affect functional differentiation and maturation of human monocyte-derived dendritic cells
复制标题
DOI：
10.4049/jimmunol.168.6.2652
复制
发表时间：
2002-03-15
影响因子：
4.4
通讯作者：
Fardel, O
中科院分区：
文献类型：
--
作者：
Laupeze, W;Amiot, L;Fardel, O
多环芳烃（PAHs），如苯并(a)芘（BP）是环境致癌物，具有强大的免疫抑制特性。为了确定这种免疫毒性的细胞基础，我们研究了多环芳烃对单核细胞来源的树突状细胞（DC）的分化、成熟和功能的影响。在GM-CSF和IL-4作用下单核细胞向DC分化的过程中，暴露于BP可显著抑制DC中CD1a、CD80和CD40等标志物的上调，但不改变细胞活力。除BP外，多环芳烃（PAHs）如二甲基苯(a)蒽和苯并蒽也会强烈改变CD1a水平。此外，在BP存在下产生的DC显示出内吞活性降低。脂多糖介导的DC成熟特征，如CD83上调和IL-12分泌，也在BP治疗中受到损害。与未处理的DC相比，bp暴露DC在混合白细胞反应中对T细胞增殖的刺激较差。与BP相反，卤代芳烃2,3,7,8-四氯二苯并-对二恶英与多环芳烃有一些共同的特征，包括与芳烃受体的相互作用，但未能在表型上改变单核细胞向DC的分化，这表明与芳烃受体的结合不能模拟多环芳烃对DC的影响。总的来说，这些数据表明，暴露于多环芳烃会抑制血液单核细胞来源的DC的体外功能分化和成熟。由于DC在免疫反应的发展中作为有效的APC发挥了主要作用，这种效应可能有助于这些环境污染物的免疫毒性。
Polycyclic aromatic hydrocarbons (PAHs) such as benzo(a)pyrene (BP) are environmental carcinogens exhibiting potent immunosuppressive properties. To determine the cellular bases of this Immunotoxicity, we have studied the effects of PAHs on differentiation, maturation, and function of monocyte-derived dendritic cells (DC). Exposure to BP during monocyte differentiation into DC upon the action of GM-CSF and IL-4 markedly inhibited the up-regulation of markers found in DC such as CD1a, CD80, and CD40, without altering cell viability. Besides BP, PAHs such as dimethylbenz(a)anthracene and benzanthracene also strongly altered CD1a levels. Moreover, DC generated in the presence of BP displayed decreased endocytic activity. Features of LPS-mediated maturation of DC, such as CD83 up-regulation and IL-12 secretion, were also Impaired in response to BP treatment. BP-exposed DC poorly stimulated T cell proliferation in mixed leukocyte reactions compared with their untreated counterparts. In contrast to BP, the halogenated arylhydrocarbon 2,3,7,8-tetrachlorodibenzo-p-dioxin, which shares some features with PAHs, including interaction with the arylhydrocarbon receptor, failed to phenotypically alter differentiation of monocytes into DC, suggesting that binding to the arylhydrocarbon receptor cannot mimic PAH effects on DC. Overall, these data demonstrate that exposure to PAHs inhibits in vitro functional differentiation and maturation of blood monocyte-derived DC. Such an effect may contribute to the immunotoxicity of these environmental contaminants due to the major role that DC play as potent APC in the development of the immune response.