Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, The Netherlands.
Pulm Pharmacol Ther. 2011 Dec;24(6):682-9. doi: 10.1016/j.pupt.2011.07.001. Epub 2011 Jul 24.
Tobacco smoke is the main factor in the etiology of lung emphysema. Generally prolonged, substantial exposure is required to develop the disease. Humic acid is a major component of cigarette smoke that accumulates in smokers' lungs over time and induces tissue damage.
To investigate whether humic acid pre-loading potentiates the development of cigarette smoke-induced lung emphysema in mice and increases IL-8 release by human monocytes.
C57BL/6J mice received humic acid or aqueous vehicle by tracheal installation on day 0 and day 7. From day 21 to day 84, the mice were exposed to cigarette smoke or clean air for 5 days/week. Twenty-four hours after the last exposure we determined leukocytes in lung lavage, heart hypertrophy and alveolar wall destruction. Human monocytes were incubated with cigarette smoke extract (CSE), humic acid or the combination overnight.
Humic acid nor cigarette smoke caused alveolar wall destruction within two months. Interestingly, the combination did induce lung emphysema. Humic acid, cigarette smoke or the combination did not change leukocyte types and numbers in lung lavage fluid, but the combination caused peribronchiolar and perivascular lymphocyte infiltration. Humic acid treatment resulted in a high proportion of alveolar macrophages heavily loaded with intracellular granula. Humic acid also induces the release of IL-8 from human monocytes and enhances the CSE-induced IL-8 release.
Humic acid deposition in the lungs potentiates the development of cigarette smoke-induced interstitial inflammation and lung emphysema. Moreover, humic acid promotes IL-8 release from human monocytes. Since humic acid accumulates steadily in the lungs of smokers, this may provide an explanation for the natural history on late onset of this disease. The model described here offers a novel way to study emphysema and may direct the search for new therapeutic approaches.
烟草烟雾是肺气肿病因学中的主要因素。通常需要长期大量暴露才能引发这种疾病。腐殖酸是香烟烟雾的主要成分，随着时间的推移在吸烟者的肺部积累，并诱导组织损伤。
研究腐殖酸预加载是否会增强香烟烟雾引起的小鼠肺气肿的发展，并增加人单核细胞中白细胞介素 8 的释放。
C57BL/6J 小鼠通过气管安装在第 0 天和第 7 天接受腐殖酸或水性载体。从第 21 天到第 84 天，小鼠每周暴露于香烟烟雾或清洁空气 5 天。最后一次暴露后 24 小时，我们确定了肺灌洗液中的白细胞、心脏肥大和肺泡壁破坏。人单核细胞用香烟烟雾提取物 (CSE)、腐殖酸或两者的混合物孵育过夜。
腐殖酸和香烟烟雾在两个月内均未引起肺泡壁破坏。有趣的是，该组合确实会引起肺气肿。腐殖酸、香烟烟雾或两者的混合物并未改变肺灌洗液中的白细胞类型和数量，但该组合导致了细支气管和小血管周围的淋巴细胞浸润。腐殖酸处理导致大量肺泡巨噬细胞中含有大量细胞内颗粒。腐殖酸还诱导人单核细胞中白细胞介素 8 的释放，并增强 CSE 诱导的白细胞介素 8 释放。
腐殖酸在肺部的沉积增强了香烟烟雾引起的间质性炎症和肺气肿的发展。此外，腐殖酸促进人单核细胞中白细胞介素 8 的释放。由于腐殖酸在吸烟者的肺部中不断积累，这可能为该疾病后期发病的自然史提供了解释。这里描述的模型为研究肺气肿提供了一种新方法，并可能为新的治疗方法的研究提供指导。
