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Histidine-rich glycoprotein promotes bacterial entrapment in clots and decreases mortality in a mouse model of sepsis.

Shannon, Oonagh LU ; Rydengård, Victoria LU ; Schmidtchen, Artur LU ; Mörgelin, Matthias LU ; Alm, Per LU ; Sørensen, Ole E LU and Björck, Lars LU (2010) In Blood 116. p.2365-2372
Abstract
Streptococcus pyogenes is a significant bacterial pathogen in humans. In this study, Histidine-rich glycoprotein (HRG), an abundant plasma protein, was found to kill S. pyogenes. Furthermore, S. pyogenes grew more efficiently in HRG deficient plasma, and clots formed in this plasma were significantly less effective at bacterial entrapment and killing. HRG deficient mice were strikingly more susceptible to S. pyogenes infection. These animals failed to control the infection at the local subcutaneous site, and abscess formation and inflammation was diminished as compared with control animals. As a result, bacterial dissemination occurred more rapidly in HRG deficient mice and they succumbed earlier and with a significantly higher mortality... (More)
Streptococcus pyogenes is a significant bacterial pathogen in humans. In this study, Histidine-rich glycoprotein (HRG), an abundant plasma protein, was found to kill S. pyogenes. Furthermore, S. pyogenes grew more efficiently in HRG deficient plasma, and clots formed in this plasma were significantly less effective at bacterial entrapment and killing. HRG deficient mice were strikingly more susceptible to S. pyogenes infection. These animals failed to control the infection at the local subcutaneous site, and abscess formation and inflammation was diminished as compared with control animals. As a result, bacterial dissemination occurred more rapidly in HRG deficient mice and they succumbed earlier and with a significantly higher mortality rate than control animals. HRG deficient mice supplemented with purified HRG gave the same phenotype as control animals, demonstrating that the lack of HRG was responsible for the increased susceptibility. The results demonstrate a previously unappreciated role for HRG as a regulator of inflammation and in the defence at the local site of bacterial infection. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Blood
volume
116
pages
2365 - 2372
publisher
American Society of Hematology
external identifiers
  • wos:000282369700025
  • pmid:20587784
  • scopus:77957726744
ISSN
1528-0020
DOI
10.1182/blood-2010-02-271858
language
English
LU publication?
yes
id
206fe1fd-bb9c-449f-8a97-a6c2d6b5be04 (old id 1645472)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20587784?dopt=Abstract
date added to LUP
2010-08-02 09:28:08
date last changed
2018-06-03 04:30:14
@article{206fe1fd-bb9c-449f-8a97-a6c2d6b5be04,
  abstract     = {Streptococcus pyogenes is a significant bacterial pathogen in humans. In this study, Histidine-rich glycoprotein (HRG), an abundant plasma protein, was found to kill S. pyogenes. Furthermore, S. pyogenes grew more efficiently in HRG deficient plasma, and clots formed in this plasma were significantly less effective at bacterial entrapment and killing. HRG deficient mice were strikingly more susceptible to S. pyogenes infection. These animals failed to control the infection at the local subcutaneous site, and abscess formation and inflammation was diminished as compared with control animals. As a result, bacterial dissemination occurred more rapidly in HRG deficient mice and they succumbed earlier and with a significantly higher mortality rate than control animals. HRG deficient mice supplemented with purified HRG gave the same phenotype as control animals, demonstrating that the lack of HRG was responsible for the increased susceptibility. The results demonstrate a previously unappreciated role for HRG as a regulator of inflammation and in the defence at the local site of bacterial infection.},
  author       = {Shannon, Oonagh and Rydengård, Victoria and Schmidtchen, Artur and Mörgelin, Matthias and Alm, Per and Sørensen, Ole E and Björck, Lars},
  issn         = {1528-0020},
  language     = {eng},
  pages        = {2365--2372},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {Histidine-rich glycoprotein promotes bacterial entrapment in clots and decreases mortality in a mouse model of sepsis.},
  url          = {http://dx.doi.org/10.1182/blood-2010-02-271858},
  volume       = {116},
  year         = {2010},
}