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Treatment of invasive streptococcal infection with a peptide derived from human high molecular weight kininogen.

Oehmcke, Sonja LU ; Shannon, Oonagh LU ; von Kockritz-Blickwede, Maren; Mörgelin, Matthias LU ; Linder, Adam LU ; Olin, Anders LU ; Björck, Lars LU and Herwald, Heiko LU (2009) In Blood 114(2). p.444-451
Abstract
Sepsis and septic shock remain an important medical problem, emphasizing the need to identify novel therapeutic opportunities. Hypovolemic hypotension, coagulation dysfunction, disturbed microcirculation, and multiorgan failure due to vascular leakage are often observed in these severe conditions. In the present study, we find that HKH20, a peptide derived from human high molecular weight kininogen (HK), down-regulates inflammatory reactions caused by Streptococcus pyogenes in a mouse model of sepsis. HK is a component of the pro-inflammatory and pro-coagulant contact system. Activation of the contact system in the bloodstream by S. pyogenes leads to massive tissue damage in the lungs of the infected mice, which eventually results in the... (More)
Sepsis and septic shock remain an important medical problem, emphasizing the need to identify novel therapeutic opportunities. Hypovolemic hypotension, coagulation dysfunction, disturbed microcirculation, and multiorgan failure due to vascular leakage are often observed in these severe conditions. In the present study, we find that HKH20, a peptide derived from human high molecular weight kininogen (HK), down-regulates inflammatory reactions caused by Streptococcus pyogenes in a mouse model of sepsis. HK is a component of the pro-inflammatory and pro-coagulant contact system. Activation of the contact system in the bloodstream by S. pyogenes leads to massive tissue damage in the lungs of the infected mice, which eventually results in the death of the animals. HKH20 inhibits activation of the contact system and protects mice with invasive S. pyogenes infection from lung damage. In combination with clindamycin treatment, the peptide also significantly prolongs the survival of infected mice. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Blood
volume
114
issue
2
pages
444 - 451
publisher
American Society of Hematology
external identifiers
  • wos:000268061700030
  • pmid:19433860
  • scopus:67651113977
ISSN
1528-0020
DOI
10.1182/blood-2008-10-182527
language
English
LU publication?
yes
id
4373b365-3549-4781-87b6-02facc69c710 (old id 1412414)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19433860?dopt=Abstract
date added to LUP
2009-06-03 12:28:13
date last changed
2017-01-01 04:47:37
@article{4373b365-3549-4781-87b6-02facc69c710,
  abstract     = {Sepsis and septic shock remain an important medical problem, emphasizing the need to identify novel therapeutic opportunities. Hypovolemic hypotension, coagulation dysfunction, disturbed microcirculation, and multiorgan failure due to vascular leakage are often observed in these severe conditions. In the present study, we find that HKH20, a peptide derived from human high molecular weight kininogen (HK), down-regulates inflammatory reactions caused by Streptococcus pyogenes in a mouse model of sepsis. HK is a component of the pro-inflammatory and pro-coagulant contact system. Activation of the contact system in the bloodstream by S. pyogenes leads to massive tissue damage in the lungs of the infected mice, which eventually results in the death of the animals. HKH20 inhibits activation of the contact system and protects mice with invasive S. pyogenes infection from lung damage. In combination with clindamycin treatment, the peptide also significantly prolongs the survival of infected mice.},
  author       = {Oehmcke, Sonja and Shannon, Oonagh and von Kockritz-Blickwede, Maren and Mörgelin, Matthias and Linder, Adam and Olin, Anders and Björck, Lars and Herwald, Heiko},
  issn         = {1528-0020},
  language     = {eng},
  number       = {2},
  pages        = {444--451},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {Treatment of invasive streptococcal infection with a peptide derived from human high molecular weight kininogen.},
  url          = {http://dx.doi.org/10.1182/blood-2008-10-182527},
  volume       = {114},
  year         = {2009},
}