Diesel exhaust particle-exposed human bronchial epithelial cells induce dendritic cell maturation
Diesel exhaust particle-exposed human bronchial epithelial cells induce dendritic cell maturation
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DOI：
10.4049/jimmunol.176.12.7431
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发表时间：
2006-06-15
影响因子：
4.4
通讯作者：
Reibman, Joan
中科院分区：
文献类型：
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作者：
Bleck, Bertram;Tse, Doris B.;Reibman, Joan
增加接触柴油机尾气颗粒 (DEP) 等空气污染物已被认为是解释过敏性疾病增加的一种机制。然而，DEP 增强过敏性和哮喘的免疫机制仍不清楚。我们假设 DEP 通过影响气道上皮细胞衍生的 DC 微环境，充当未成熟树突状细胞 (DC) 成熟的佐剂。未成熟的单核细胞来源的 DC (iMDDC) 在暴露于 DEP (0.001-100 μg/ml) 后未能经历表型（CD80、CD83、CD86）或功能（T 细胞激活）成熟。相比之下，用 DEP 处理的人支气管上皮细胞 (HBEC) 的原代培养物诱导 iMDDC 表型成熟（CD83 表达增加 2.6 +/- 0.1 倍，n = 4，p < 0.05）和功能成熟（T 细胞活化增加 2.6 +/- 0.2 倍，n = 4，p < 0.05）。 iMDDC 的功能成熟是由源自 DEP 处理的 HBEC 的条件培养基诱导的，并且在含有 DEP 处理的 HBEC 和针对 GM-CSF 或 GM-CSF 靶向小干扰 RNA 的阻断抗体的培养物中受到抑制。这些数据表明，DEP 通过 HBEC 衍生的 GM-CSF 介导的上皮细胞-DC 相互作用诱导不依赖于 Ag 的 DC 成熟。尽管直流电极化可能需要额外的信号，但这些数据表明环境污染物改变气道免疫反应的新机制。
Increased exposure to air pollutants such as diesel exhaust particles (DEP) has been proposed as one mechanism to explain the rise in allergic disorders. However, the immunologic mechanisms by which DEP enhance allergic sensitization and asthma remain unclear. We hypothesized that DEP act as an adjuvant for immature dendritic cell (DC) maturation via its effect on airway epithelial cell-derived microenvironment for DC. Immature monocyte-derived DC (iMDDC) failed to undergo phenotypic (CD80, CD83, CD86) or functional (T cell activation) maturation in response to exposure to DEP (0.001-100 mu g/ml). In contrast, primary cultures of human bronchial epithelial cells (HBEC) treated with DEP induced iMDDC phenotypic maturation (2.6 +/- 0.1-fold increase in CD83 expression, n = 4, p < 0.05) and functional maturation (2.6 +/- 0.2-fold increase in T cell activation, n = 4, p < 0.05). Functional maturation of iMDDC was induced by conditioned medium derived from DEP-treated HBEC, and was inhibited in cultures with DEP-treated HBEC and blocking Abs against GM-CSF, or GM-CSF-targeted small interfering RNA. These data suggest that DEP induce Ag-independent DC maturation via epithelial cell-DC interactions mediated by HBEC-derived GM-CSF. Although additional signals may be required for polarization of DC, these data suggest a novel mechanism by which environmental pollutants alter airway immune responses.