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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4528212
- author
- Westman, Johannes
LU
; Smeds, Emanuel
LU
; Johansson, Linda
; Mörgelin, Matthias
LU
; Olin, Anders
LU
; Malmström, Erik
LU
; Linder, Adam
LU
and Herwald, Heiko
LU
- organization
- publishing date
- 2014
- 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
- pmid:24942226
- ISSN
- 1662-811X
- DOI
- 10.1159/000363348
- project
- p33 project
- 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
- 2016-04-01 11:14:57
- date last changed
- 2022-01-26 06:30:04
@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 = {{https://lup.lub.lu.se/search/files/2504964/5156630.pdf}},
doi = {{10.1159/000363348}},
volume = {{6}},
year = {{2014}},
}