Shore Stephanie A, Terry Raya D, Flynt Lesley, Xu Aimin, Hug Christopher
Physiology Program, Department of Environmental Health, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA.
J Allergy Clin Immunol. 2006 Aug;118(2):389-95. doi: 10.1016/j.jaci.2006.04.021. Epub 2006 May 30.
Epidemiologic data indicate an increased incidence of asthma in the obese.
Because serum levels of the insulin-sensitizing and anti-inflammatory adipokine adiponectin are reduced in obese individuals, we sought to determine whether exogenous adiponectin can attenuate allergic airway responses.
We sensitized and challenged BALB/cJ mice with ovalbumin (OVA). Alzet micro-osmotic pumps were implanted in the mice to deliver continuous infusions of buffer or adiponectin (1.0 microg/g/d), which resulted in an approximate 60% increase in serum adiponectin levels. Two days later, mice were challenged with aerosolized saline or OVA once per day for 3 days. Mice were examined 24 hours after the last challenge.
OVA challenge increased airway responsiveness to intravenous methacholine, bronchoalveolar lavage fluid cells, and T(H)2 cytokine levels. Importantly, each of these responses to OVA was reduced in adiponectin- versus buffer-treated mice. OVA challenge caused a 30% reduction in serum adiponectin levels and a corresponding decrease in adipose tissue adiponectin mRNA expression. OVA challenge also decreased pulmonary mRNA expression of each of 3 proposed adiponectin-binding proteins, adiponectin receptor 1, adiponectin receptor 2, and T-cadherin.
Our results indicate that serum adiponectin is reduced during pulmonary allergic reactions and that adiponectin attenuates allergic airway inflammation and airway hyperresponsiveness in mice.
The data suggest that adiponectin might play a role in the relationship between obesity and asthma.
流行病学数据表明肥胖人群中哮喘发病率增加。
由于肥胖个体中胰岛素增敏和抗炎脂肪因子脂联素的血清水平降低，我们试图确定外源性脂联素是否能减轻过敏性气道反应。
我们用卵清蛋白（OVA）对BALB/cJ小鼠进行致敏和激发。将Alzet微渗透泵植入小鼠体内，以持续输注缓冲液或脂联素（1.0微克/克/天），这导致血清脂联素水平大约增加60%。两天后，小鼠每天接受一次雾化盐水或OVA激发，共3天。在最后一次激发后24小时对小鼠进行检查。
OVA激发增加了气道对静脉注射乙酰甲胆碱的反应性、支气管肺泡灌洗液细胞数量以及T(H)2细胞因子水平。重要的是，与缓冲液处理的小鼠相比，脂联素处理的小鼠对OVA的这些反应均有所降低。OVA激发导致血清脂联素水平降低30%，同时脂肪组织脂联素mRNA表达相应下降。OVA激发还降低了3种推测的脂联素结合蛋白（脂联素受体1、脂联素受体2和T-钙黏蛋白）在肺中的mRNA表达。
我们的结果表明，在肺部过敏反应期间血清脂联素降低，并且脂联素可减轻小鼠的过敏性气道炎症和气道高反应性。
这些数据表明脂联素可能在肥胖与哮喘的关系中起作用。
