Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/103671
Title: An antimicrobial helix A-derived peptide of heparin cofactor II blocks endotoxin responses in vivo
Authors: Papareddy, Praveen
Kalle, Martina
Morgelin, Matthias
Schmidtchen, Artur
Malmsten, Martin
Singh, Shalini
Keywords: DRNTU::Science::Medicine
Issue Date: 2014
Source: Papareddy, P., Kalle, M., Singh, S., Mörgelinc, M., Schmidtchen, A., & Malmsten, M. (2014). An antimicrobial helix A-derived peptide of heparin cofactor II blocks endotoxin responses in vivo. Biochimica et Biophysica Acta (BBA) - Biomembranes, 1838(5), 1225-1234.
Series/Report no.: Biochimica et biophysica acta (BBA) - biomembranes
Abstract: Host defense peptides are key components of the innate immune system, providing multi-facetted responses to invading pathogens. Here, we describe that the peptide GKS26 (GKSRIQRLNILNAKFAFNLYRVLKDQ), corresponding to the A domain of heparin cofactor II (HCII), ameliorates experimental septic shock. The peptide displays antimicrobial effects through direct membrane disruption, also at physiological salt concentration and in the presence of plasma and serum. Biophysical investigations of model lipid membranes showed the antimicrobial action of GKS26 to be mirrored by peptide incorporation into, and disordering of, bacterial lipid membranes. GKS26 furthermore binds extensively to bacterial lipopolysaccharide (LPS), as well as its endotoxic lipid A moiety, and displays potent anti-inflammatory effects, both in vitro and in vivo. Thus, for mice challenged with ip injection of LPS, GKS26 suppresses pro-inflammatory cytokines, reduces vascular leakage and infiltration in lung tissue, and normalizes coagulation. Together, these findings suggest that GKS26 may be of interest for further investigations as therapeutic against severe infections and septic shock.
URI: https://hdl.handle.net/10356/103671
http://hdl.handle.net/10220/19290
ISSN: 0005-2736
DOI: 10.1016/j.bbamem.2014.01.026
Rights: © 2014 Elsevier B.V. This is the author created version of a work that has been peer reviewed and accepted for publication by Biochimica et Biophysica Acta (BBA) - Biomembranes, Elsevier B.V. It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [http://dx.doi.org/10.1016/j.bbamem.2014.01.026].
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

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