Acute exposure to diesel exhaust increases IL-8 and GRO-α production in healthy human airways
Acute exposure to diesel exhaust increases IL-8 and GRO-α production in healthy human airways
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DOI：
10.1164/ajrccm.161.2.9905052
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发表时间：
2000-02-01
影响因子：
24.7
通讯作者：
Frew, AJ
中科院分区：
文献类型：
--
作者：
Salvi, SS;Nordenhall, C;Frew, AJ
我们之前已经证明，短期暴露于柴油废气（DE） 1小时可诱导健康人类志愿者气道中明显的白细胞浸润，包括中性粒细胞、淋巴细胞和肥大细胞，同时几种炎症介质增加。我们假设DE诱导的白细胞浸润和各种炎症反应是由气道组织和管腔内常驻细胞产生的趋化因子和细胞因子增强介导的。为了研究这一点，15名健康人类志愿者在两个不同的场合暴露于稀释的DE和空气中，每次暴露1小时，每次暴露6小时后进行纤维支气管镜检查，获得支气管内活检和支气管洗涤（BW）细胞。利用逆转录酶/聚合酶链反应酶联免疫吸附法（RT-PCR ELISA），一种新的、灵敏的技术来定量细胞因子mRNA基因转录物的相对数量，并用免疫组织化学染色和计算机辅助图像分析来定量支气管组织中细胞因子蛋白的表达。我们已经证明，DE增强了支气管组织和BW细胞中白细胞介素-8 （IL-8）的基因转录，同时增加了支气管上皮中IL-8和生长调节癌基因α (gro - α)蛋白的表达，并伴有支气管组织中IL-5 mRNA基因转录的增加趋势。在此Lime点DE暴露后，支气管组织或BW细胞中白细胞介素- 1b （IL-1 β）、肿瘤坏死因子- α (tnf - α)、干扰素γ (ifn - γ)和粒细胞巨噬细胞集落刺激因子（GM-CSF）的基因转录水平均无显著变化。这些观察结果提示了de诱导气道白细胞浸润的潜在机制，并为流行病学研究中观察到的环境颗粒物水平与各种呼吸健康结局指标之间的关联提供了可能的解释。
We have previously demonstrated that short-term exposure to diesel exhaust (DE) for 1 h induced marked leukocytic infiltration in the airways of healthy human volunteers involving neutrophils, lymphocytes, and mast cells along with increases in several inflammatory mediators. We hypothesized that the leukocyte infiltration and the various inflammatory responses induced by DE were mediated by enhanced chemokine and cytokine production by resident: cells of the airway tissue and lumen. To investigate this, 15 healthy human volunteers were exposed to diluted DE and air on two separate occasions for 1 h each in an exposure chamber, Fiberoptic bronchoscopy was performed 6 h after each exposure to obtain endobronchial biopsies and bronchial wash (BW) cells. Using reverse transcriptase/polymerase chain reaction enzyme-linked immunosorbent assay (RT-PCR ELISA), a novel and sensitive technique to quantify relative amounts of cytokine mRNA gene transcripts, and immunohistochemical staining with computer-assisted image analysis to quantify expression of cytokine protein in the bronchial tissue, we have demonstrated that DE enhanced gene transcription of interleukin-8 (IL-8) in the bronchial tissue and BW cells along with increases in IL-8 and growth-regulated oncogene-alpha (GRO-alpha) protein expression in the bronchial epithelium, and an accompanying trend toward an increase in IL-5 mRNA gene transcripts in the bronchial tissue. There were no significant changes in the gene transcript levels of interleukin-1B (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), interferon gamma (IFN-gamma), and granulocyte macrophage colony-stimulating factor (GM-CSF) either in the bronchial tissue or BW cells after DE exposure at this Lime point, These observations suggest an underlying mechanism for DE-induced airway leukocyte infiltration and offer a possible explanation for the association observed between ambient levels of particulate matter and various respiratory health outcome indices noted in epidemiological studies.