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The contact system-a novel branch of innate immunity generating antibacterial peptides.

Frick, Inga-Maria LU ; Åkesson, Per LU ; Herwald, Heiko LU orcid ; Mörgelin, Matthias LU ; Malmsten, Martin LU ; Nagler, Dorit K and Björck, Lars LU (2006) In EMBO Journal 25(23). p.5569-5578
Abstract
Activation of the contact system has two classical consequences: initiation of the intrinsic pathway of coagulation, and cleavage of high molecular weight kininogen (HK) leading to the release of bradykinin, a potent proinflammatory peptide. In human plasma, activation of the contact system at the surface of significant bacterial pathogens was found to result in further HK processing and bacterial killing. A fragment comprising the D3 domain of HK is generated, and within this fragment a sequence of 26 amino acids is mainly responsible for the antibacterial activity. A synthetic peptide covering this sequence kills several bacterial species, also at physiological salt concentration, as effectively as the classical human antibacterial... (More)
Activation of the contact system has two classical consequences: initiation of the intrinsic pathway of coagulation, and cleavage of high molecular weight kininogen (HK) leading to the release of bradykinin, a potent proinflammatory peptide. In human plasma, activation of the contact system at the surface of significant bacterial pathogens was found to result in further HK processing and bacterial killing. A fragment comprising the D3 domain of HK is generated, and within this fragment a sequence of 26 amino acids is mainly responsible for the antibacterial activity. A synthetic peptide covering this sequence kills several bacterial species, also at physiological salt concentration, as effectively as the classical human antibacterial peptide LL-37. Moreover, in an animal model of infection, inhibition of the contact system promotes bacterial dissemination and growth. These data identify a novel and important role for the contact system in the defence against invasive bacterial infection. (Less)
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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
bacterial killing, antibacterial peptides, contact system, innate, immunity
in
EMBO Journal
volume
25
issue
23
pages
5569 - 5578
publisher
Oxford University Press
external identifiers
  • wos:000242890900012
  • scopus:33751579326
ISSN
1460-2075
DOI
10.1038/sj.emboj.7601422
language
English
LU publication?
yes
id
0405b2d5-8f97-4b79-ab7e-3650af7cc666 (old id 163334)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17093496&dopt=Abstract
date added to LUP
2016-04-01 16:41:22
date last changed
2025-10-14 10:57:02
@article{0405b2d5-8f97-4b79-ab7e-3650af7cc666,
  abstract     = {{Activation of the contact system has two classical consequences: initiation of the intrinsic pathway of coagulation, and cleavage of high molecular weight kininogen (HK) leading to the release of bradykinin, a potent proinflammatory peptide. In human plasma, activation of the contact system at the surface of significant bacterial pathogens was found to result in further HK processing and bacterial killing. A fragment comprising the D3 domain of HK is generated, and within this fragment a sequence of 26 amino acids is mainly responsible for the antibacterial activity. A synthetic peptide covering this sequence kills several bacterial species, also at physiological salt concentration, as effectively as the classical human antibacterial peptide LL-37. Moreover, in an animal model of infection, inhibition of the contact system promotes bacterial dissemination and growth. These data identify a novel and important role for the contact system in the defence against invasive bacterial infection.}},
  author       = {{Frick, Inga-Maria and Åkesson, Per and Herwald, Heiko and Mörgelin, Matthias and Malmsten, Martin and Nagler, Dorit K and Björck, Lars}},
  issn         = {{1460-2075}},
  keywords     = {{bacterial killing; antibacterial peptides; contact system; innate; immunity}},
  language     = {{eng}},
  number       = {{23}},
  pages        = {{5569--5578}},
  publisher    = {{Oxford University Press}},
  series       = {{EMBO Journal}},
  title        = {{The contact system-a novel branch of innate immunity generating antibacterial peptides.}},
  url          = {{http://dx.doi.org/10.1038/sj.emboj.7601422}},
  doi          = {{10.1038/sj.emboj.7601422}},
  volume       = {{25}},
  year         = {{2006}},
}