Department of Medicine, Univ. of California, San Diego, La Jolla, 92093-0635, USA.
Am J Physiol Lung Cell Mol Physiol. 2010 Dec;299(6):L834-42. doi: 10.1152/ajplung.00326.2009. Epub 2010 Oct 8.
Adiponectin is a cytokine with both proinflammatory and anti-inflammatory properties that is expressed in epithelial cells in the airway in chronic obstructive pulmonary disease-emphysema (COPD-E). To determine whether adiponectin modulates levels of lung inflammation in tobacco smoke-induced COPD-E, we used a mouse model of COPD-E in which either adiponectin-deficient or wild-type (WT) mice were exposed to tobacco smoke for 6 mo. Outcomes associated with tobacco smoke-induced COPD-E were quantitated including lung inflammation [bronchoalveolar lavage (BAL) and total and differential cell count], lung mediators of inflammation (cytokines and chemokines), air space enlargement (i.e., linear intercept), and lung function (tissue elastance) in the different groups of mice. Whereas exposure of WT mice to tobacco smoke for 6 mo induced significant lung inflammation (increased total BAL cells, neutrophils, and macrophages), adiponectin-deficient mice had minimal BAL inflammation when exposed to tobacco smoke for 6 mo. In addition, whereas chronic tobacco-exposed WT mice had significantly increased levels of lung mediators of inflammation [i.e., TNF-α, keratinocyte-derived chemokine (KC), and adiponectin] as well as significantly increased air space enlargement (increased linear intercept) and decreased tissue elastance, exposure of adiponectin-deficient mice to chronic tobacco smoke resulted in no further increase in lung mediators, air space enlargement, or tissue elastance. In vitro studies demonstrated that BAL macrophages derived from adiponectin-deficient mice incubated in media containing tobacco smoke expressed minimal TNF-α or KC compared with BAL macrophages from WT mice. These studies suggest that adiponectin plays an important proinflammatory role in tobacco smoke-induced COPD-E.
脂联素是一种细胞因子，具有促炎和抗炎特性，在慢性阻塞性肺疾病-肺气肿（COPD-E）的气道上皮细胞中表达。为了确定脂联素是否调节烟草烟雾诱导的 COPD-E 中的肺部炎症水平，我们使用了一种 COPD-E 的小鼠模型，其中脂联素缺陷型或野生型（WT）小鼠暴露于烟草烟雾 6 个月。定量评估与烟草烟雾诱导的 COPD-E 相关的结果，包括肺炎症[支气管肺泡灌洗（BAL）和总细胞计数和分类细胞计数]、肺部炎症介质（细胞因子和趋化因子）、气腔扩大（即线性截距）和不同组小鼠的肺功能（组织弹性）。虽然 WT 小鼠暴露于烟草烟雾 6 个月会引起明显的肺部炎症（增加总 BAL 细胞、中性粒细胞和巨噬细胞），但脂联素缺陷型小鼠在暴露于烟草烟雾 6 个月时 BAL 炎症最小。此外，慢性暴露于烟草的 WT 小鼠的肺部炎症介质[即 TNF-α、角质细胞衍生的趋化因子（KC）和脂联素]水平显著增加，气腔扩大（线性截距增加）和组织弹性降低，而脂联素缺陷型小鼠暴露于慢性烟草烟雾不会导致肺部炎症介质、气腔扩大或组织弹性进一步增加。体外研究表明，与 WT 小鼠的 BAL 巨噬细胞相比，来自脂联素缺陷型小鼠的在含有烟草烟雾的培养基中孵育的 BAL 巨噬细胞表达的 TNF-α 或 KC 最少。这些研究表明，脂联素在烟草烟雾诱导的 COPD-E 中发挥重要的促炎作用。
