Inflammatory time course after quartz instillation -: Role of tumor necrosis factor-α and particle surface
Inflammatory time course after quartz instillation -: Role of tumor necrosis factor-α and particle surface
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DOI：
10.1165/rcmb.2003-0300oc
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发表时间：
2004-09-01
影响因子：
6.4
通讯作者：
Borm, PJA
中科院分区：
文献类型：
--
作者：
Albrecht, C;Schins, RPF;Borm, PJA
炎症被认为是石英诱导的纤维化和癌变的关键因素，而颗粒表面特性被认为是导致这些病理变化的重要特征。为了评价表面修饰对急性和亚慢性炎症的影响，雌性Wistar大鼠气管内注入2 mg天然石英，或涂覆聚乙烯吡啶-N-氧化物或乳酸铝的石英。肺毒性、炎症和氧化应激的各种指标在注入天然石英后3、7、21和90d被发现增强。染石英组大鼠肺泡巨噬细胞和肺上皮细胞核因子-kappaB(NF-kappaB)免疫染色增强，全肺匀浆中IkappaBalpha水平降低。这两种表面修饰都被发现抑制了天然石英所观察到的大部分影响。用石英处理动物的灌洗液和石英处理的巨噬细胞的条件培养液处理大鼠肺上皮细胞后，在体外也观察到了核因子-kappaB的激活，这些作用似乎至少部分地不依赖于肿瘤坏死因子a。总之，石英暴露后持续的亚慢性炎症反应似乎是颗粒表面驱动的，并与肺泡巨噬细胞和肺上皮细胞中的核因子-kappaB激活有关。
Inflammation has been suggested as the key factor in the development of quartz-induced fibrosis and carcinogenesis, and particle surface properties are argued as an important characteristic responsible for these pathologic alterations. To evaluate the effect of surface modification on acute and subchronic inflammation, female Wistar rats were intratracheally instilled with 2 mg native quartz, or quartz coated either with polyvinyl-pyridine-N-oxide or with aluminium lactate. Various markers of lung toxicity, inflammation, and oxidative stress were found to be enhanced at 3, 7, 21, and 90 d after instillation of native quartz. Quartz-treated animals also showed enhanced immunostaining of nuclear factor-kappaB (NF-kappaB) in alveolar macrophages and lung epithelium, as well as reduced IkappaBalpha levels in whole lung homogenate. Both surface modifications were found to inhibit most of the effects as observed with native quartz. NF-kappaB activation was also observed in vitro in rat lung epithelial cells following treatment with lavage fluid from quartz-treated animals, as well as with conditioned medium of quartz-treated macrophages, and these effects appeared to be at least partly tumor necrosis factor-a-independent. In conclusion, the persistent subchronic inflammatory lung response after quartz exposure appears to be particle surface-driven and is associated with NF-kappaB activation in both alveolar macrophages and the lung epithelium.