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Treatment with p33 Curtails Morbidity and Mortality in a Histone-Induced Murine Shock Model.

Westman, Johannes LU ; Smeds, Emanuel LU ; Johansson, Linda; Mörgelin, Matthias LU ; Olin, Anders LU ; Malmström, Erik LU ; Linder, Adam LU and Herwald, Heiko LU (2014) In Journal of Innate Immunity 6(6). p.819-830
Abstract
Collateral damage caused by extracellular histones has an immediate impact on morbidity and mortality in many disease models. A significant increase in the levels of extracellular histones is seen in critically ill patients with trauma and sepsis. We showed that histones are released from necrotic cells in patients with invasive skin infections. Under in vitro conditions, endogenous p33, an endothelial surface protein also known as the gC1q receptor, interacts with histones released from damaged endothelial cells. Functional analyses have revealed that recombinantly expressed p33 completely neutralizes the harmful features of histones, i.e. hemolysis of erythrocytes, lysis of endothelial cells and platelet aggregation. We also noted that... (More)
Collateral damage caused by extracellular histones has an immediate impact on morbidity and mortality in many disease models. A significant increase in the levels of extracellular histones is seen in critically ill patients with trauma and sepsis. We showed that histones are released from necrotic cells in patients with invasive skin infections. Under in vitro conditions, endogenous p33, an endothelial surface protein also known as the gC1q receptor, interacts with histones released from damaged endothelial cells. Functional analyses have revealed that recombinantly expressed p33 completely neutralizes the harmful features of histones, i.e. hemolysis of erythrocytes, lysis of endothelial cells and platelet aggregation. We also noted that mice treated with a sublethal dose of histones developed severe signs of hemolysis, thrombocytopenia and lung tissue damage already 10 min after inoculation. These complications were fully counteracted when p33 was administered together with the histones. Moreover, application of p33 significantly improved survival in mice receiving an otherwise lethal dose of histones. Together, our data suggest that treatment with p33 is a promising therapeutic approach in severe infectious diseases. © 2014 S. Karger AG, Basel. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
in
Journal of Innate Immunity
volume
6
issue
6
pages
819 - 830
publisher
Karger
external identifiers
  • pmid:24942226
  • wos:000343642800010
  • scopus:84908614438
ISSN
1662-811X
DOI
10.1159/000363348
language
English
LU publication?
yes
id
3e9bc689-9267-4e55-a27a-1cf6c57a197f (old id 4528212)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24942226?dopt=Abstract
date added to LUP
2014-07-06 13:17:00
date last changed
2017-07-23 03:33:21
@article{3e9bc689-9267-4e55-a27a-1cf6c57a197f,
  abstract     = {Collateral damage caused by extracellular histones has an immediate impact on morbidity and mortality in many disease models. A significant increase in the levels of extracellular histones is seen in critically ill patients with trauma and sepsis. We showed that histones are released from necrotic cells in patients with invasive skin infections. Under in vitro conditions, endogenous p33, an endothelial surface protein also known as the gC1q receptor, interacts with histones released from damaged endothelial cells. Functional analyses have revealed that recombinantly expressed p33 completely neutralizes the harmful features of histones, i.e. hemolysis of erythrocytes, lysis of endothelial cells and platelet aggregation. We also noted that mice treated with a sublethal dose of histones developed severe signs of hemolysis, thrombocytopenia and lung tissue damage already 10 min after inoculation. These complications were fully counteracted when p33 was administered together with the histones. Moreover, application of p33 significantly improved survival in mice receiving an otherwise lethal dose of histones. Together, our data suggest that treatment with p33 is a promising therapeutic approach in severe infectious diseases. © 2014 S. Karger AG, Basel.},
  author       = {Westman, Johannes and Smeds, Emanuel and Johansson, Linda and Mörgelin, Matthias and Olin, Anders and Malmström, Erik and Linder, Adam and Herwald, Heiko},
  issn         = {1662-811X},
  language     = {eng},
  number       = {6},
  pages        = {819--830},
  publisher    = {Karger},
  series       = {Journal of Innate Immunity},
  title        = {Treatment with p33 Curtails Morbidity and Mortality in a Histone-Induced Murine Shock Model.},
  url          = {http://dx.doi.org/10.1159/000363348},
  volume       = {6},
  year         = {2014},
}