Allergic airway responses in obese mice
Allergic airway responses in obese mice
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DOI：
10.1164/rccm.200702-323oc
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发表时间：
2007-10-01
影响因子：
24.7
通讯作者：
Shore, Stephanie A.
中科院分区：
文献类型：
--
作者：
Johnston, Richard A.;Zhu, Ming;Shore, Stephanie A.
基本原理：流行病学数据表明哮喘的发病率增加在obesit.Objectives：以确定是否肥胖小鼠过敏原致敏和challenge.Methods：瘦，野生型（C57 BL/6），肥胖ob/ob，和肥胖db/db小鼠过敏卵清蛋白（OVA），然后用雾化卵清蛋白或磷酸盐缓冲盐水（PBS）的挑战后，表现出增强的肺反应。用强迫振荡法测定乙酰甲胆碱引起的肺总阻力（RL）的变化。收集血液，进行支气管肺泡灌洗（BAL），并收获肺细胞因子的表达通过实时逆转录-聚合酶链reaction.Measurements和主要结果：OVA的挑战增加了基线R-L在ob/ob，但不是野生型，小鼠和气道反应性是更大的ob/ob比野生型小鼠，无论挑战。与PBS相比，OVA激发导致BALF细胞数量增加，肺Th 2细胞因子表达增加，血清IgE升高。与野生型小鼠相比，从OVA攻击的ob/ob小鼠中回收的BALF细胞显著较少，而血清IgE水平在ob/ob小鼠中显著升高。BALIF和肺Th 2细胞因子表达在ob/ob与野生型小鼠中没有差异。气道反应性是更大的db/db与野生型小鼠，无论挑战，和OVA引起气道高反应性db/db，但不是野生型小鼠，尽管减少BALF细胞在OVA挑战的db/db与野生型migrations.Conclusions：这些结果表明，肥胖增强OVA诱导的肺阻力和血清IgE的变化，这些变化是不是增加的Th 2型气道炎症的结果。
Rationale: Epidemiologic data indicate an increased incidence of asthma in the obese.Objectives: To determine whether obese mice exhibit augmented pulmonary responses after allergen sensitization and challenge.Methods: Lean, wild-type (C57BL/6), obese ob/ob, and obese db/db mice were sensitized to ovalbumin (OVA), and then challenged with aerosolized OVA or phosphate-buffered saline (PBS). Changes in total pulmonary resistance (RL) induced by intravenous methacholine were measured by forced oscillation. Blood was collected, bronchoalveolar lavage (BAL) was performed, and lungs were harvested for measurement of cytokine expression by real-time reverse transcription-polymerase chain reaction.Measurements and Main Results: OVA challenge increased baseline R-L in ob/ob, but not wild-type, mice, and airway responsiveness was greater in ob/ob than wild-type mice, regardless of the challenge. Compared with PBS, OVA challenge caused an increase in the number of BAL fluid (BALF) cells, an increase in lung Th2 cytokine expression, and an increase in serum IgE. Significantly fewer BALF cells were recovered from OVA-challenged ob/ob versus wild-type mice, whereas serum IgE levels were elevated significantly more in ob/ob versus wild-type mice. BALIF and lung Th2 cytokine expression was not different in ob/ob versus wild-type mice. Airway responsiveness was greater in db/db versus wild-type mice, regardless of the challenge, and OVA caused airway hyperresponsiveness in db/db but not wild-type mice, despite reduced BALF cells in OVA-challenged db/db versus wild-type mice.Conclusions: These results demonstrate that obesity enhances OVA-induced changes in pulmonary resistance and serum IgE and that these changes are not the result of increased Th2 type airway inflammation.