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Glycosaminoglycans inhibit the antibacterial activity of LL-37 in biological fluids

Baranska-Rybak, W; Sonesson, Andreas LU ; Nowicki, R and Schmidtchen, Artur LU (2006) In Journal of Antimicrobial Chemotherapy 57(2). p.260-265
Abstract
Objectives: The antibacterial activity of antimicrobial peptides is influenced by various factors such as salt content, pH and the presence of proteins. In this study, we explored the antibacterial action of the human cathelicidin LL-37 in physiologically relevant conditions, i.e. various human wound fluids, human plasma fractions and serum. Methods: Radial diffusion assays using Staphylococcus aureus and Escherichia coli were employed for the study of antibacterial effects of LL-37 in the presence of 12 different wound fluids, citrate-, heparin- or EDTA-plasma, or human serum. Glycosaminoglycan content of wound fluids was determined by an Alcian Blue-binding assay. Protein content of wound fluids was measured by the Bradford method. A... (More)
Objectives: The antibacterial activity of antimicrobial peptides is influenced by various factors such as salt content, pH and the presence of proteins. In this study, we explored the antibacterial action of the human cathelicidin LL-37 in physiologically relevant conditions, i.e. various human wound fluids, human plasma fractions and serum. Methods: Radial diffusion assays using Staphylococcus aureus and Escherichia coli were employed for the study of antibacterial effects of LL-37 in the presence of 12 different wound fluids, citrate-, heparin- or EDTA-plasma, or human serum. Glycosaminoglycan content of wound fluids was determined by an Alcian Blue-binding assay. Protein content of wound fluids was measured by the Bradford method. A slot-binding assay was used to study the effects of inhibitors on the interaction between LL-37 and glycosaminoglycans. Results: Five of twelve wound fluids derived from acute wounds showed marked inhibitory effects on the antibacterial action of LL-37. The inhibition was significantly correlated with high glycosaminoglycan content in wound fluid. Analogous to these findings, heparin-plasma strongly inhibited the antibacterial effect of LL-37. The interaction between LL-37 and glycosaminoglycans was abrogated by the cationic polymers DEAE-dextran and chitosan, yielding increased activity of LL-37. Conclusions: Glycosaminoglycan-rich biological fluids inhibit the antibacterial effects of LL-37. Furthermore, polycations that bind to glycosaminoglycans increase the antibacterial activities of endogenous antimicrobial peptides in glycosaminoglycan-containing biological fluids. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
plasma, wound fluids, bacteria, serum, antibacterial peptides
in
Journal of Antimicrobial Chemotherapy
volume
57
issue
2
pages
260 - 265
publisher
Oxford University Press
external identifiers
  • wos:000234967400015
  • pmid:16387752
  • scopus:31544463056
ISSN
1460-2091
DOI
10.1093/jac/dki460
language
English
LU publication?
yes
id
c8c1962a-0ec3-43c2-8e7f-598ea23a68cb (old id 419433)
date added to LUP
2007-09-25 13:27:50
date last changed
2019-07-02 01:38:47
@article{c8c1962a-0ec3-43c2-8e7f-598ea23a68cb,
  abstract     = {Objectives: The antibacterial activity of antimicrobial peptides is influenced by various factors such as salt content, pH and the presence of proteins. In this study, we explored the antibacterial action of the human cathelicidin LL-37 in physiologically relevant conditions, i.e. various human wound fluids, human plasma fractions and serum. Methods: Radial diffusion assays using Staphylococcus aureus and Escherichia coli were employed for the study of antibacterial effects of LL-37 in the presence of 12 different wound fluids, citrate-, heparin- or EDTA-plasma, or human serum. Glycosaminoglycan content of wound fluids was determined by an Alcian Blue-binding assay. Protein content of wound fluids was measured by the Bradford method. A slot-binding assay was used to study the effects of inhibitors on the interaction between LL-37 and glycosaminoglycans. Results: Five of twelve wound fluids derived from acute wounds showed marked inhibitory effects on the antibacterial action of LL-37. The inhibition was significantly correlated with high glycosaminoglycan content in wound fluid. Analogous to these findings, heparin-plasma strongly inhibited the antibacterial effect of LL-37. The interaction between LL-37 and glycosaminoglycans was abrogated by the cationic polymers DEAE-dextran and chitosan, yielding increased activity of LL-37. Conclusions: Glycosaminoglycan-rich biological fluids inhibit the antibacterial effects of LL-37. Furthermore, polycations that bind to glycosaminoglycans increase the antibacterial activities of endogenous antimicrobial peptides in glycosaminoglycan-containing biological fluids.},
  author       = {Baranska-Rybak, W and Sonesson, Andreas and Nowicki, R and Schmidtchen, Artur},
  issn         = {1460-2091},
  keyword      = {plasma,wound fluids,bacteria,serum,antibacterial peptides},
  language     = {eng},
  number       = {2},
  pages        = {260--265},
  publisher    = {Oxford University Press},
  series       = {Journal of Antimicrobial Chemotherapy},
  title        = {Glycosaminoglycans inhibit the antibacterial activity of LL-37 in biological fluids},
  url          = {http://dx.doi.org/10.1093/jac/dki460},
  volume       = {57},
  year         = {2006},
}