Syed, Mobin (2009) Role of human ?-defensins in human burn wounds. Doctoral thesis, University of Westminster.
Background - Burns is a complex condition requiring assessment and addressing of both the wound and the patient in a holistic way. In spite of tremendous improvements in burn care, infection continues to remain an important cause of morbidity and mortality. Human ? Defensins (HBD) are a group of recently discovered antimicrobial peptides. The main subtypes include HBD1, 2 and 3 and are individually known to have other functions apart from being anti-microbial. Some of these are inherently expressed while others are induced in response to microbial challenge. Aims - The aim of the current PhD was to understand the pattern of expression of HBDs in acute burns, their source of expression, and factors influencing the expression, with a view to use these peptides as therapeutic agents in future. Methods - The expression of HBD1, 2 & 3 was determined at mRNA and protein levels in acute burn wounds of different burn durations, using real time rt-PCR and immunohistochemistry, respectively. The influence of type and quantity of bacteria, contribution from blood cells and the influence of stress on HBD expression was determined in separate clinical situations similar to those seen in major burns. Results - The results show that HBD1, 2 and 3 mRNA is highly expressed in both early and late burns, but a parallel increase is not reciprocated at protein levels. The bacteria isolated from the burn wounds showed a trend changing from colonising organisms to more resistant forms in time, however no significant correlation with HBD was established. Peripheral blood cells produced HBD in response to inflammatory mediator’s in-vivo, thus suggesting to a possible contribution of HBD 1, 2 and 3 from blood cells in granulating burn wounds. There was no down regulation of HBD1, 2 and 3 in the presence of increased cortisol levels – a reflection of heightened stress as seen in burns. HBD1 and 3 mRNA expressions showed an early up-regulation, followed by elevation in HBD2 mRNA levels. There was no HBD2 mRNA and protein expression in keloid tissue specimens from various parts of the body. The absence of HBD2 – a unique intrinsic peptide with an ability to trigger the anti-fibrotic cytokines suggests to the possibility that HBD’s are implicated in the pathogenesis of keloids, which are usually associated with burn scars. Conclusion - The studies suggest a possible role of HBD in the pathogenesis of burn wounds and the potential to use these as therapeutic peptides to prevent infections and scarring associated with burns.
|Item Type:||Thesis (Doctoral)|
|Subjects:||University of Westminster > Science and Technology > Life Sciences, School of (No longer in use)|
|Depositing User:||Miss Nina Watts|
|Date Deposited:||17 Aug 2010 09:33|
|Last Modified:||17 Aug 2010 09:33|
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