In vitro effects on macrophages induced by noncytotoxic doses of silica particles possibly relevant to ambient exposure
In vitro effects on macrophages induced by noncytotoxic doses of silica particles possibly relevant to ambient exposure
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DOI：
10.1016/j.envres.2003.11.004
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发表时间：
2004-09-01
影响因子：
8.3
通讯作者：
Paoletti, L
中科院分区：
文献类型：
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作者：
Balduzzi, M;Diociaiuti, M;Paoletti, L
RAW 246.7巨噬细胞系在体外暴露于可呼吸大小的陈化结晶二氧化硅颗粒24小时，剂量范围从15个/2×10(6)个细胞开始，这是环境暴露个人呼吸道中巨噬细胞的真实暴露水平。用于实验的颗粒样品是为了模拟环境中结晶二氧化硅颗粒的某些方面而准备的：尺寸分布、形态和表面反应性。我们的目的是确定与环境暴露相当的无毒石英负荷是否能够诱导巨噬细胞激活和吞噬能力受损，这些因素改变了肺应对增加的颗粒物负荷(如在高污染期间发生)或感染的能力，并通过释放生物活性化合物(细胞因子、活性氧、NO、异前列腺素)影响局部和全身反应。将RAW 264.7细胞暴露在老化的二氧化硅颗粒中，可诱导巨噬细胞活化(扫描电子显微镜观察到的形态特征以及肿瘤坏死因子-α和白介素6的释放)，并抑制试验颗粒的吞噬功能，即使在非细胞毒性剂量下也是如此。二氧化硅处理后细胞吞噬功能的降低是剂量依赖性的，表现为非吞噬细胞数量的增加，同时活跃吞噬细胞数量的减少。我们评估了老化的二氧化硅颗粒诱导的氧化应激，量化了处理细胞培养液中的过氧化产物(8-异前列腺素)，发现在低剂量下有强烈的释放。异前列腺素是一个复杂的化合物家族，已被用作人体疾病中脂质过氧化的体内标志物，但据我们所知，从未被评估与空气颗粒物暴露的关系。过氧化脂质参与了炎症反应中的各种细胞事件，异前列腺素也被认为在呼吸道和肺血管平滑肌以及血小板上发挥重要的生物学作用。(C)2003 Elsevier Inc.保留所有权利。
The RAW 246.7 macrophage cell line was exposed in vitro to aged crystalline silica particles of respirable size for 24 h at a range of doses starting from 15 mug/2 x 10(6) Cells, which is a realistic exposure level of macrophages in the airways of ambiently exposed individuals. The particle sample used for the experiments was prepared to mimic some aspects of ambient crystalline silica particles: size distribution, morphology, and surface reactivity. Our purpose was to determine whether a nontoxic quartz load comparable to that of ambient exposure would be able to induce macrophage activation and impairment of the phagocytic ability, factors altering the lung's capacity to deal with increased particle loads (as occurs during high-pollution episodes) or infections and affecting the local and systemic responses through the release of biologically active compounds (cytokines, reactive oxygen species, NO, isoprostanes). Exposure of RAW 264.7 cells to aged silica particles induced macrophage activation (evidenced by the morphological features observed with scanning electron microscopy and by the release of TNF-alpha and IL-6) and impairment of phagocytosis of test particles, even at noncytotoxic doses. The reduction of the phagocytic function of the cells after silica treatment was dose-dependent, as evidenced by an increase of the population of unphagocytic cells, paralleled by a decrease of the actively phagocytizing cell population. We evaluated the oxidative stress induced by aged silica particles, quantifying the peroxidation products (8-isoprostanes) in the culture media of treated cells, and found a strong release at low doses. Isoprostanes are a complex family of compounds which have been used as in vivo markers of lipid peroxidation in human disorders, but that, as far as we know, have never been evaluated in relation to airborne particulate matter exposure. Lipid peroxides are involved in various cellular events in the inflammatory response, and isoprostanes are also supposed to exert important biological actions on airway and pulmonary vascular smooth muscles and on platelets. (C) 2003 Elsevier Inc. All rights reserved.