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Acute exposure to wood smoke from incomplete combustion--indications of cytotoxicity.
Particle and Fibre Toxicology ( IF 10 ) Pub Date : 2015-10-29 , DOI: 10.1186/s12989-015-0111-7
Ala Muala 1 , Gregory Rankin 1 , Maria Sehlstedt 1 , Jon Unosson 1 , Jenny A Bosson 1 , Annelie Behndig 1 , Jamshid Pourazar 1 , Robin Nyström 2 , Esbjörn Pettersson 2 , Christoffer Bergvall 3 , Roger Westerholm 3 , Pasi I Jalava 4 , Mikko S Happo 4 , Oskari Uski 4 , Maija-Riitta Hirvonen 4 , Frank J Kelly 5 , Ian S Mudway 5 , Anders Blomberg 1 , Christoffer Boman 2 , Thomas Sandström 1
Affiliation  

Smoke from combustion of biomass fuels is a major risk factor for respiratory disease, but the underlying mechanisms are poorly understood. The aim of this study was to determine whether exposure to wood smoke from incomplete combustion would elicit airway inflammation in humans. Fourteen healthy subjects underwent controlled exposures on two separate occasions to filtered air and wood smoke from incomplete combustion with PM1 concentration at 314 μg/m3 for 3 h in a chamber. Bronchoscopy with bronchial wash (BW), bronchoalveolar lavage (BAL) and endobronchial mucosal biopsies was performed after 24 h. Differential cell counts and soluble components were analyzed, with biopsies stained for inflammatory markers using immunohistochemistry. In parallel experiments, the toxicity of the particulate matter (PM) generated during the chamber exposures was investigated in vitro using the RAW264.7 macrophage cell line. Significant reductions in macrophage, neutrophil and lymphocyte numbers were observed in BW (p < 0.01, <0.05, <0.05, respectively) following the wood smoke exposure, with a reduction in lymphocytes numbers in BAL fluid (<0.01. This unexpected cellular response was accompanied by decreased levels of sICAM-1, MPO and MMP-9 (p < 0.05, <0.05 and <0.01). In contrast, significant increases in submucosal and epithelial CD3+ cells, epithelial CD8+ cells and submucosal mast cells (p < 0.01, <0.05, <0.05 and <0.05, respectively), were observed after wood smoke exposure. The in vitro data demonstrated that wood smoke particles generated under these incomplete combustion conditions induced cell death and DNA damage, with only minor inflammatory responses. Short-term exposure to sooty PAH rich wood smoke did not induce an acute neutrophilic inflammation, a classic hallmark of air pollution exposure in humans. While minor proinflammatory lymphocytic and mast cells effects were observed in the bronchial biopsies, significant reductions in BW and BAL cells and soluble components were noted. This unexpected observation, combined with the in vitro data, suggests that wood smoke particles from incomplete combustion could be potentially cytotoxic. Additional research is required to establish the mechanism of this dramatic reduction in airway leukocytes and to clarify how this acute response contributes to the adverse health effects attributed to wood smoke exposure. NCT01488500

中文翻译:

不完全燃烧导致的木材烟雾急性暴露——细胞毒性的迹象。

生物质燃料燃烧产生的烟雾是呼吸道疾病的主要风险因素,但其潜在机制却知之甚少。本研究的目的是确定暴露于不完全燃烧的木材烟雾是否会引起人类气道炎症。14 名健康受试者在两个不同的场合受控暴露于过滤后的空气和不完全燃烧产生的木材烟雾,PM1 浓度为 314 μ​​g/m3,在一个室内持续 3 小时。24小时后进行支气管镜检查,包括支气管冲洗液(BW)、支气管肺泡灌洗液(BAL)和支气管内粘膜活检。分析差异细胞计数和可溶性成分,并使用免疫组织化学对活检组织的炎症标志物进行染色。在平行实验中,使用 RAW264.7 巨噬细胞系在体外研究了在腔室暴露期间产生的颗粒物 (PM) 的毒性。暴露于木烟后,BW 中的巨噬细胞、中性粒细胞和淋巴细胞数量显着减少(分别为 p < 0.01、<0.05、<0.05),BAL 液中的淋巴细胞数量减少(<0.01。这种意想不到的细胞反应是伴随着 sICAM-1、MPO 和 MMP-9 水平下降(p < 0.05、<0.05 和 <0.01)。相比之下,黏膜下和上皮 CD3+ 细胞、上皮 CD8+ 细胞和黏膜下肥大细胞显着增加(p < 0.01, <0.05,<0.05 和 <0.05,分别),在木烟暴露后观察到。体外数据表明,在这些不完全燃烧条件下产生的木烟颗粒会导致细胞死亡和 DNA 损伤,只有轻微的炎症反应。短期暴露于富含多环芳烃的烟灰木烟不会诱发急性中性粒细胞炎症,这是人类空气污染暴露的典型标志。虽然在支气管活检中观察到轻微的促炎淋巴细胞和肥大细胞作用,但注意到 BW 和 BAL 细胞以及可溶性成分的显着减少。这一出乎意料的观察结果与体外数据相结合,表明来自不完全燃烧的木烟颗粒可能具有潜在的细胞毒性。需要进一步的研究来确定气道白细胞急剧减少的机制,并阐明这种急性反应如何导致木材烟雾暴露造成的不良健康影响。NCT01488500
更新日期:2015-10-29
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