An antimicrobial helix A-derived peptide of heparin cofactor II blocks endotoxin responses in vivo.
(2014) In Biochimica et Biophysica Acta 1838(5). p.1225-1234- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4334782
- author
- Papareddy, Praveen LU ; Kalle, Martina LU ; Singh, Shalini ; Mörgelin, Matthias LU ; Schmidtchen, Artur LU and Malmsten, Martin LU
- organization
- publishing date
- 2014
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Biochimica et Biophysica Acta
- volume
- 1838
- issue
- 5
- pages
- 1225 - 1234
- publisher
- Elsevier
- external identifiers
-
- pmid:24522010
- wos:000334008100004
- scopus:84894536600
- pmid:24522010
- ISSN
- 0006-3002
- DOI
- 10.1016/j.bbamem.2014.01.026
- language
- English
- LU publication?
- yes
- id
- a781cf87-3320-4ddc-b1a2-32d9906aeb99 (old id 4334782)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/24522010?dopt=Abstract
- date added to LUP
- 2016-04-01 14:08:51
- date last changed
- 2022-02-19 17:17:15
@article{a781cf87-3320-4ddc-b1a2-32d9906aeb99, 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.}}, author = {{Papareddy, Praveen and Kalle, Martina and Singh, Shalini and Mörgelin, Matthias and Schmidtchen, Artur and Malmsten, Martin}}, issn = {{0006-3002}}, language = {{eng}}, number = {{5}}, pages = {{1225--1234}}, publisher = {{Elsevier}}, series = {{Biochimica et Biophysica Acta}}, title = {{An antimicrobial helix A-derived peptide of heparin cofactor II blocks endotoxin responses in vivo.}}, url = {{https://lup.lub.lu.se/search/files/3815245/4611578.pdf}}, doi = {{10.1016/j.bbamem.2014.01.026}}, volume = {{1838}}, year = {{2014}}, }