20-HETE mediates ozone-induced, neutrophil-independent airway hyper-responsiveness in mice.
20-HETE mediates ozone-induced, neutrophil-independent airway hyper-responsiveness in mice.
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DOI：
10.1371/journal.pone.0010235
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发表时间：
2010-04-20
期刊：
影响因子：
3.7
通讯作者：
Panettieri RA
中科院分区：
文献类型：
--
作者：
Cooper PR;Mesaros AC;Zhang J;Christmas P;Stark CM;Douaidy K;Mittelman MA;Soberman RJ;Blair IA;Panettieri RA
臭氧是一种已知会引起气道高反应性 (AHR) 的污染物，会增加阻塞性气道疾病和哮喘患者的发病率和死亡率。我们假设氧化脂质在小鼠气道中介导体内臭氧诱导的 AHR。雄性 BALB/c 小鼠暴露于臭氧（3 或 6 ppm）或过滤空气（对照）2 小时。暴露后立即或 16 小时后制备含有肺内气道（~0.01 mm2 管腔面积）的精密切割肺切片（PCLS；250 µm 厚度）。 24小时后，气道收缩为卡巴胆碱（CCh）。然后通过测量相对于基线的气道腔面积来计算 Log EC50 和 Emax 值。在平行研究中，在臭氧暴露前 18 小时，对幼鼠腹腔注射地塞米松 (2.5 mg/kg) 或 1-氨基苯并三唑 (ABT) (50 mg/kg)。提前 2 小时给予吲哚美辛 (10 mg/kg)。对臭氧暴露小鼠和对照小鼠的支气管肺泡灌洗 (BAL) 液中的细胞计数、细胞因子水平和用于脂质分析的液相色谱-质谱 (LC-MS) 进行了评估。臭氧急性诱导 CCh 的 AHR。地塞米松或吲哚美辛对臭氧引起的AHR影响不大；而细胞色素 P450 抑制剂 ABT 则显着减弱气道敏感性。来自臭氧暴露动物的 BAL 液体中的中性粒细胞或白细胞介素 (IL)-6 水平并未增加，在与首次 PCLS 体外孵育后，气道敏感性增加。与此同时，使用 LC-MS 还发现氧化脂质显着增加，其中 20-HETE 增加，但 ABT 治疗后减少。这些数据表明，臭氧可不依赖于炎症而急性诱导 AHR 转化为 CCh，并且对类固醇治疗或环氧合酶 (COX) 抑制不敏感。暴露于臭氧的小鼠的支气管肺泡灌洗液模拟了体内臭氧暴露的影响，这种影响与氧化脂质的显着增加有关。 20-HETE 在介导急性臭氧诱导的 AHR 中发挥着关键作用。
Ozone, a pollutant known to induce airway hyper-responsiveness (AHR), increases morbidity and mortality in patients with obstructive airway diseases and asthma. We postulate oxidized lipids mediate in vivo ozone-induced AHR in murine airways. Male BALB/c mice were exposed to ozone (3 or 6 ppm) or filtered air (controls) for 2 h. Precision cut lung slices (PCLS; 250 µm thickness) containing an intrapulmonary airway (∼0.01 mm2 lumen area) were prepared immediately after exposure or 16 h later. After 24 h, airways were contracted to carbachol (CCh). Log EC50 and Emax values were then calculated by measuring the airway lumen area with respect to baseline. In parallel studies, dexamethasone (2.5 mg/kg), or 1-aminobenzotriazol (ABT) (50 mg/kg) were given intraperitoneal injection to naïve mice 18 h prior to ozone exposure. Indomethacin (10 mg/kg) was administered 2 h prior. Cell counts, cytokine levels and liquid chromatography-mass spectrometry (LC-MS) for lipid analysis were assessed in bronchoalveolar lavage (BAL) fluid from ozone exposed and control mice. Ozone acutely induced AHR to CCh. Dexamethasone or indomethacin had little effect on the ozone-induced AHR; while, ABT, a cytochrome P450 inhibitor, markedly attenuated airway sensitivity. BAL fluid from ozone exposed animals, which did not contain an increase in neutrophils or interleukin (IL)-6 levels, increased airway sensitivity following in vitro incubation with a naïve PCLS. In parallel, significant increases in oxidized lipids were also identified using LC-MS with increases of 20-HETE that were decreased following ABT treatment. These data show that ozone acutely induces AHR to CCh independent of inflammation and is insensitive to steroid treatment or cyclooxygenase (COX) inhibition. BAL fluid from ozone exposed mice mimicked the effects of in vivo ozone exposure that were associated with marked increases in oxidized lipids. 20-HETE plays a pivotal role in mediating acute ozone-induced AHR.
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影响因子：
10.4
作者：
Chen C;Arjomandi M;Balmes J;Tager I;Holland N
通讯作者：
Holland N
DOI：
10.1152/ajplung.00381.2002
发表时间：
2003-09-01
影响因子：
4.9
作者：
Cloutier, M;Campbell, S;Rousseau, E
通讯作者：
Rousseau, E
影响因子：
5
作者：
Medina-Ramón, M;Zanobetti, A;Schwartz, J
通讯作者：
Schwartz, J
DOI：
10.1164/ajrccm/138.1.140
发表时间：
1988-07-01
期刊：
AMERICAN REVIEW OF RESPIRATORY DISEASE
影响因子：
--
作者：
EVANS, TW;BROKAW, JJ;MCDONALD, DM
通讯作者：
MCDONALD, DM
影响因子：
4.8
作者：
Christmas, P;Tolentino, K;Soberman, RJ
通讯作者：
Soberman, RJ