Comparative airway inflammatory response of normal volunteers to ozone and lipopolysaccharide challenge.

Comparative airway inflammatory response of normal volunteers to ozone and lipopolysaccharide challenge.
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DOI:
10.3109/08958371003610966
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发表时间:
2010-07
影响因子:
2.1
通讯作者:
Peden DB
Peden DB
中科院分区:
医学4区
文献类型:
--
作者:
Hernandez ML;Harris B;Lay JC;Bromberg PA;Diaz-Sanchez D;Devlin RB;Kleeberger SR;Alexis NE;Peden DB

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臭氧和脂多糖(LPS)是环境污染物,在健康和哮喘个体中都有不良健康影响。作者和其他人已经表明,吸入臭氧和LPS都会诱导气道嗜酸性粒细胞。基于这些相似性,作者检验了共同的生物学因素决定对这两种不同药物的反应的假设。15名健康的非哮喘志愿者在进行间歇性适度运动的同时,接受了百万分之0.4的臭氧暴露2小时。这些相同的受试者用20,000个LPS单位的临床中心参考LPS进行吸入性LPS激发,这两个激发阶段至少间隔1个月。在每次暴露前24 h和暴露后4-6 h采集诱导痰。通过流式细胞术测量,评估痰液的总细胞计数和分类细胞计数以及细胞表面蛋白的表达。测定痰液上清液中的细胞因子浓度。臭氧和LPS激发增强痰中性粒细胞和受试者的反应显着相关(R = 0.73)彼此。臭氧通过修饰单核细胞(CD 14,人类白细胞抗原[HLA]-DR,CD 11b)和巨噬细胞(CD 11b,HLA-DR)对细胞表面蛋白的总体影响更大,而LPS仅修饰单核细胞上的CD 14和HLA-DR。然而,LPS显著增加了白细胞介素(IL)-1β,IL-6和肿瘤坏死因子(TNF)-α,臭氧攻击后未见显著增加。健康志愿者的臭氧和LPS暴露在气道中诱导类似的中性粒细胞反应;然而,先天免疫反应的下游激活不同,表明氧化剂与细菌空气污染物可能由不同的机制介导。
Ozone and lipopolysaccharide (LPS) are environmental pollutants with adverse health effects noted in both healthy and asthmatic individuals. The authors and others have shown that inhalation of ozone and LPS both induce airway neutrophilia. Based on these similarities, the authors tested the hypothesis that common biological factors determine response to these two different agents. Fifteen healthy, nonasthmatic volunteers underwent a 0.4 part per million ozone exposure for 2 h while performing intermittent moderate exercise. These same subjects underwent an inhaled LPS challenge with 20,000 LPS units of Clinical Center Reference LPS, with a minimum of 1 month separating these two challenge sessions. Induced sputum was obtained 24 h before and 4–6 h after each exposure session. Sputum was assessed for total and differential cell counts and expression of cell surface proteins as measured by flow cytometry. Sputum supernatants were assayed for cytokine concentration. Both ozone and LPS challenge augmented sputum neutrophils and subjects’ responses were significantly correlated (R = .73) with each other. Ozone had greater overall influence on cell surface proteins by modifying both monocytes (CD14, human leukocyte antigen [HLA]-DR, CD11b) and macrophages (CD11b, HLA-DR) versus LPS where CD14 and HLA-DR were modified only on monocytes. However, LPS significantly increased interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, with no significant increases seen after ozone challenge. Ozone and LPS exposure in healthy volunteers induce similar neutrophil responses in the airways; however, downstream activation of innate immune responses differ, suggesting that oxidant versus bacterial air pollutants may be mediated by different mechanisms.
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DOI: 10.1164/rccm.2112064
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影响因子: 24.7
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