uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
An antimicrobial helix A-derived peptide of heparin cofactor II blocks endotoxin responses in vivo
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
Show others and affiliations
2014 (English)In: Biochimica et Biophysica Acta - Biomembranes, ISSN 0005-2736, E-ISSN 1879-2642, Vol. 1838, no 5, 1225-1234 p.Article in journal (Refereed) Published
Abstract [en]

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 (GKSRIQRLNILNAKFAFNLYRVLICDQ), 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.

Place, publisher, year, edition, pages
2014. Vol. 1838, no 5, 1225-1234 p.
Keyword [en]
Antimicrobial peptide, Lipopolysaccharide, lipid A, Membrane
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-224562DOI: 10.1016/j.bbamem.2014.01.026ISI: 000334008100004OAI: oai:DiVA.org:uu-224562DiVA: diva2:717974
Available from: 2014-05-19 Created: 2014-05-14 Last updated: 2014-05-19Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Search in DiVA

By author/editor
Singh, ShaliniMalmsten, Martin
By organisation
Department of Pharmacy
In the same journal
Biochimica et Biophysica Acta - Biomembranes
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar

Altmetric score

Total: 161 hits
ReferencesLink to record
Permanent link

Direct link