Acute inflammatory responses in the airways and peripheral blood after short-term exposure to diesel exhaust in healthy human volunteers
Acute inflammatory responses in the airways and peripheral blood after short-term exposure to diesel exhaust in healthy human volunteers
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DOI：
10.1164/ajrccm.159.3.9709083
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发表时间：
1999-03-01
影响因子：
24.7
通讯作者：
Frew, A
中科院分区：
文献类型：
--
作者：
Salvi, S;Blomberg, A;Frew, A
多项流行病学研究表明，环境空气中的颗粒物 (PM) 水平与心血管和呼吸系统死亡率和发病率的增加之间存在一致的关联。柴油机尾气 (DE) 除了产生其他污染物外，也是世界大多数地区 PM 污染的主要来源。尽管流行病学证据很充分，但目前还没有确定的生物学机制来解释 PM 对人类的毒性。为了确定 DE 对人类呼吸道的影响，我们将 IS 健康人类志愿者在受控条件下暴露于空气和稀释的 DE 中 1 小时，并进行间歇性运动。在每次暴露之前和之后测量肺功能。每次暴露后 6 小时进行血液采样和支气管镜检查，以获得气道灌洗液和支气管内活检。虽然标准肺功能指标在 DE 暴露后没有变化，但气道灌洗中的中性粒细胞和 B 淋巴细胞显着增加，同时组胺和纤连蛋白也增加。 DE暴露后6小时获得的支气管活检显示中性粒细胞、肥大细胞、CD4+和CD8+T淋巴细胞显着增加，同时内皮粘附分子ICAM-1和VCAM-1上调，支气管组织中LFA-1+细胞数量增加。DE暴露后外周血中中性粒细胞和血小板显着增加。这项研究表明，在高环境浓度下，急性短期 DE 暴露会在健康人类志愿者中产生明确且显着的全身和肺部炎症反应，而标准肺功能测量结果会低估这种反应。
Several epidemiologic studies have demonstrated a consistent association between levels of particulate matter (PM) in the ambient air with increases in cardiovascular and respiratory mortality and morbidity. Diesel exhaust (DE), in addition to generating other pollutants, Is a major contributor to PM pollution in most places in the world. Although the epidemiologic evidence is strong, there are as yet no established biological mechanisms to explain the toxicity of PM in humans. To determine the Impact of DE on human airways, we exposed IS healthy human volunteers to air and diluted DE under controlled conditions for 1 h with intermittent exercise. Lung functions were measured before and after each exposure. Blood sampling and bronchoscopy were performed 6 h after each exposure to obtain airway lavages and endobronchial biopsies. While standard lung function measures did not change following DE exposure, there was a significant increase in neutrophils and B lymphocytes in airway lavage, along with increases in histamine and fibronectin. The bronchial biopsies obtained 6 h after DE exposure showed a significant increase in neutrophils, mast cells, CD4+ and CD8+ T lymphocytes along with upregulation of the endothelial adhesion molecules ICAM-1 and VCAM-1, with increases in the numbers of LFA-1+ cells in the bronchial tissue.. Significant increases in neutrophils and platelets were observed In peripheral blood following DE exposure. This study demonstrates that at high ambient concentrations, acute short-term DE exposure produces a well-defined and marked systemic and pulmonary inflammatory response In healthy human volunteers, which Is underestimated by standard lung function measurements.