Matsuse Hiroto, Fukushima Chizu, Shimoda Terufumi, Sadahiro Asai, Kohno Shigeru
Second Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
Novartis Found Symp. 2007;285:97-106; discussion 106-9, 198-9. doi: 10.1002/9780470511848.ch7.
The purpose of the present study was to determine the effects of acetaldehyde on airway smooth muscle constriction and inflammation. An oral ethanol provocation test was performed in Japanese asthmatics to measure pulmonary function, blood ethanol, acetaldehyde and histamine. Acetaldehyde dehydrogenase 2 (ALDH2) genotype was determined by polymerase chain reaction (PCR) and ethanol patch test. Human bronchi and mast cells were stimulated with acetaldehyde in vitro. Mite allergen-sensitized mice were inoculated with intranasal acetaldehyde. Approximately half the asthmatic subjects developed bronchoconstriction with concomitant increases in blood acetaldehyde and histamine, which was associated with genetically reducedALDH2 activities. In vitro acetaldehyde stimulation induces bronchoconstriction and degranulation of human mast cells. It also induced granulocyte macrophage colony stimulating factor (GM-CSF) production and nuclear factor (NF)-kappaB activation in human bronchi and increased mite allergen-sensitized allergic inflammation in a murine model of asthma. We conclude that acetaldehyde has potential effects on human airway by two distinct mechanisms. As a metabolite of alcohol, its elevation following alcohol consumption induces airway mast cells to release histamine, which results in exacerbation of asthma in susceptible populations. And as an air pollutant contained in cigarette smoke, for example, its inhalation potentially increases airway inflammation.
本研究的目的是确定乙醛对气道平滑肌收缩和炎症的影响。在日本哮喘患者中进行口服乙醇激发试验，以测量肺功能、血液中的乙醇、乙醛和组胺。通过聚合酶链反应（PCR）和乙醇贴片试验确定乙醛脱氢酶2（ALDH2）基因型。在体外用乙醛刺激人支气管和肥大细胞。用鼻内注射乙醛的方法接种螨过敏原致敏的小鼠。大约一半的哮喘患者出现支气管收缩，同时血液中的乙醛和组胺增加，这与遗传上降低的ALDH2活性有关。体外乙醛刺激可诱导人肥大细胞的支气管收缩和脱颗粒。它还能诱导人支气管中粒细胞巨噬细胞集落刺激因子（GM-CSF）的产生和核因子（NF）-κB的激活，并增加哮喘小鼠模型中螨过敏原致敏的过敏性炎症。我们得出结论，乙醛通过两种不同的机制对人类气道有潜在影响。作为酒精的一种代谢产物，饮酒后其水平升高会诱导气道肥大细胞释放组胺，这会导致易感人群哮喘加重。例如，作为香烟烟雾中含有的一种空气污染物，吸入乙醛可能会增加气道炎症。
