Shu Qiang, Shi Zhuo, Zhao ZhengYan, Chen Zhi, Yao HangPing, Chen QiXing, Hoeft Andreas, Stuber Frank, Fang XiangMing
Children's Hospital, School of Medicine and National Key Laboratory of Infection Disease, Zhejiang University, Hangzhou, China.
Shock. 2006 Oct;26(4):365-71. doi: 10.1097/01.shk.0000224722.65929.58.
Beta-defensin-2 (BD-2), a small cationic antimicrobial peptide, was first described to be an inducible defensin at the epithelial surfaces. In vitro studies have demonstrated that it may play a pivotal role in the anti-inflammatory immune response in addition to its antimicrobial activity. The purpose of this study was to evaluate the effect of overexpression of BD-2 on lung injury to crudely investigate whether the function of BD-2 in the lung attributed to both antimicrobial action and modulation of the immune response. Recombinant adenovirus carrying an expression cassette of rat BD-2 or control adenovirus carrying empty vector was administered intratracheally to Sprague-Dawley rats 48 h before performing acute lung injury, which was induced either by Pseudomonas aeruginosa infection or by cecal ligation and double puncture (2CLP). In vivo antimicrobial activity of BD-2, histological changes of the lungs in both infectious and 2CLP models, pulmonary intracellular adhesion molecule-1 protein level, as well as the 7-day survival rate in the latter model were determined. Amounts of the P. aeruginosa in the lung with BD-2 overexpression were significantly lower compared with that in controls (2.87+/-0.76x10(4) colony-forming units [CFU]/mL vs. 2.49+/-0.74x10(6) CFU/mL, P<0.05). Overexpression of BD-2 reduced alveolar damage, interstitial edema, and infiltration of neutrophils in both models. Furthermore, in the 2CLP model, recombinant BD-2 not only significantly decreased protein levels of intracellular adhesion molecule-1 in lung tissue at 24, 36, and 72 h after 2CLP (P<0.05), but also significantly improved the survival of rats (P<0.05). The CFU of abdominal bacteria was comparable to that in the control rats (P>0.05). Therefore, overexpression of BD-2 protects against P. aeruginosa pneumonia and 2CLP-induced lung injury based on its antimicrobial and anti-inflammatory activities, respectively. Modulating the expression level of BD-2 may serve as an approach to attenuate lung injury.
β-防御素-2（BD-2）是一种小阳离子抗菌肽，最初被描述为上皮表面的诱导性防御素。体外研究表明，它除了具有抗菌活性外，还可能在抗炎免疫反应中起关键作用。本研究的目的是评估BD-2过表达对肺损伤的影响，以初步探究BD-2在肺中的功能是否归因于抗菌作用和免疫反应调节。在对Sprague-Dawley大鼠进行急性肺损伤（由铜绿假单胞菌感染或盲肠结扎和双穿刺（2CLP）诱导）前48小时，经气管内给予携带大鼠BD-2表达盒的重组腺病毒或携带空载体的对照腺病毒。测定了BD-2的体内抗菌活性、感染模型和2CLP模型中肺的组织学变化、肺细胞内黏附分子-1蛋白水平以及后者模型中的7天生存率。与对照组相比，BD-2过表达的肺中铜绿假单胞菌数量显著降低（2.87±0.76×10⁴菌落形成单位[CFU]/mL对2.49±0.74×10⁶CFU/mL，P<0.05）。BD-2过表达减轻了两种模型中的肺泡损伤、间质水肿和中性粒细胞浸润。此外，在2CLP模型中，重组BD-2不仅在2CLP后24、36和72小时显著降低肺组织中细胞内黏附分子-1的蛋白水平（P<0.05），还显著提高了大鼠的生存率（P<0.05）。腹部细菌的CFU与对照大鼠相当（P>0.05）。因此，BD-2过表达分别基于其抗菌和抗炎活性，对铜绿假单胞菌肺炎和2CLP诱导的肺损伤具有保护作用。调节BD-2的表达水平可能是减轻肺损伤的一种方法。
