PROTECTION AGAINST PSEUDOMONAS AERUGINOSA PNEUMONIA AND SEPSIS-INDUCED LUNG INJURY BY OVEREXPRESSION of β-DEFENSIN-2 IN RATS

Abstract

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.

Genomic variations within DEFB1 are associated with the susceptibility to and the fatal outcome of severe sepsis in Chinese Han population

“…5 Meanwhile, in vivo study showed a protective role of overexpressed bdefensin 2 against sepsis via anti-inflammation activity. 31 Studies have shown that DEFB4 and DEFB103 as well as DEFB104 were polymorphic in copy number variation, [20][21][22] and the genomic copy number of DEFB4 correlated with the level of its transcript. 20 Copy number polymorphism of defensin may have a crucial role in inflammatory disease, which has been demonstrated in Crohn's disease.…”

“…Consistent with this view were the findings indicating that defensins did suppress the release of proinflammatory cytokines and adhesion molecules in vivo. 29,31 Thus, DEFB1 could both play a direct antimicrobial role and have a modulating effect on the inflammatory response. In summary, DEFB1 plays an important role in the host immune response to severe sepsis.…”

Candida albicans Airway Exposure Primes the Lung Innate Immune Response against Pseudomonas aeruginosa Infection through Innate Lymphoid Cell Recruitment and Interleukin-22-Associated Mucosal Response

“…IL-22 has recently been implicated in the preservation of epithelial integrity through its action on intercellular junctions and the synthesis of antimicrobial peptides (26,30). Among antimicrobial peptides, ␤-defensin-2 and cathelicidin have been reported to play a pivotal role in the control of P. aeruginosa infection (40)(41)(42). Since both antimicrobial peptides were strongly potentiated by C. albicans exposure, this mechanism could therefore participate in the protection.…”

Prognostic Value of Plasma Human β-Defensin 2 Level on Short-Term Clinical Outcomes in Patients With Community-Acquired Pneumonia: A Preliminary Study

“…[6][7][8] The majority of prior studies focused on the pathophysiological effect of HBD-2 in respiratory infection, demonstrating activation of HBD-2 biosynthesis and release into the airway and plasma via bacterial or foreign microorganisms, and inflammatory cytokines stimulation following pneumonia or other lower-respiratory-tract infection. [9][10][11][12][13][14][15][16] However, few studies have examined the clinical implication of the elevated HBD-2 in community-acquired pneumonia (CAP), and whether HBD-2 predicts clinical outcomes in CAP. Therefore, this study evaluated the association between plasma HBD-2 concentration on admission and 30-day clinical outcomes in patients with CAP.…”