The Host Defence Peptide LL-37 is Susceptible to Proteolytic Degradation by Wound Fluid Isolated from Foot Ulcers of Diabetic Patients

Maelıosa T.C. McCrudden, Denise T. F. McLean, Mei Zhou, Julia Shaw, Gerard J. Linden, Chris R. Irwin, Fionnuala T. Lundy*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

The pleiotropic effects of host defence peptides (HDPs), including the ability to kill microorganisms, enhance re-epithelialisation and increase angiogenesis, indicates a role for these important peptides as potential therapeutic agents in the treatment of chronic, non-healing wounds. However, the maintenance of peptide integrity, through resistance to degradation by the array of proteinases present at the wound site, is a prerequisite for clinical success. In this study we explored the degradation of exogenous LL-37, one such HDP, by wound fluid from diabetic foot ulcers to determine its susceptibility to proteolytic degradation. Our results suggest that LL-37 is unstable in the diabetic foot ulcer microenvironment. Following overnight treatment with wound fluid, LL-37 was completely degraded. Analysis of cleavage sites suggested potential involvement of both host- and bacterial-derived proteinases. The degradation products were shown to retain some antibacterial activity against Pseudomonas aeruginosa but were inactive against Staphylococcus aureus. In conclusion, our data suggest that stabilising selected peptide bonds within the sequence of LL-37 would represent an avenue for future research prior to clinical studies to address its potential as an exogenously-applied therapeutic in diabetic wounds. 

Original languageEnglish
Pages (from-to)457-464
Number of pages8
JournalInternational Journal of Peptide Research and Therapeutics
Volume20
Issue number4
Early online date17 May 2014
DOIs
Publication statusPublished - Dec 2014

Keywords

  • Cathelicidin
  • Diabetes
  • Fluid
  • MALDI-TOF
  • Proteinase
  • Wound

ASJC Scopus subject areas

  • Analytical Chemistry
  • Drug Discovery
  • Molecular Medicine
  • Bioengineering
  • Biochemistry

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