Protection against Pseudomonas Aeruginosa pneumonia and sepsis-induced lung injury by overexpression of β-defensin-2 in rats

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 purpo...

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Bibliographic Details
Published in:Shock (Augusta, Ga.) Ga.), 2006-10, Vol.26 (4), p.365-371
Main Authors: QIANG SHU, ZHUO SHI, ZHENGYAN ZHAO, ZHI CHEN, HANGPING YAO, QIXING CHEN, HOEFT, Andreas, STUBER, Frank, XIANGMING FANG
Format: Article
Language:English
Subjects:
Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
Animals
beta-Defensins - biosynthesis
beta-Defensins - genetics
Biological and medical sciences
Cell Line
Cercopithecus aethiops
COS Cells
Emergency and intensive care: infection, septic shock
Emergency and intensive respiratory care
Genetic Therapy
Humans
Intensive care medicine
Medical sciences
Pneumonia, Bacterial - pathology
Pneumonia, Bacterial - prevention & control
Pseudomonas aeruginosa
Pseudomonas Infections - pathology
Pseudomonas Infections - prevention & control
Rats
Rats, Sprague-Dawley
Sepsis - pathology
Sepsis - therapy
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Summary: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
ISSN:1073-2322
1540-0514
DOI:10.1097/01.shk.0000224722.65929.58