JAC Advance Access published online on December 30, 2005
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dki460
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1 Department of Dermatology, Venereology and Allergology, Medical University of Gda
* To whom correspondence should be addressed. 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.
Received March 2, 2005
Revised October 19, 2005
Accepted November 26, 2005
Original article
Glycosaminoglycans inhibit the antibacterial activity of LL-37 in biological fluids
W. Bara
ska-Rybak 1 * 
,
A. Sonesson 2 ,
R. Nowicki 3,
and
A. Schmidtchen 2
sk, D
binki 7 Street, 80-288 Gdask, Poland; Dermatology and Venereology, Department of Clinical Sciences, Biomedical Center B14, Tornavägen 10, S-22184 Lund, Sweden
2 Dermatology and Venereology, Department of Clinical Sciences, Biomedical Center B14, Tornavägen 10, S-22184 Lund, Sweden
3 Department of Dermatology, Venereology and Allergology, Medical University of Gdask, Dbinki 7 Street, 80-288 Gdask, Poland
W. Baraska-Rybak, E-mail: wbaranska{at}pf.pl
Abstract Dr Baraska-Rybak and Dr Sonesson contributed equally to this work.
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