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Streptococcal cysteine proteinase releases kinins: a novel virulence mechanism

Herwald, Heiko LU ; Collin, Mattias LU ; Muller-Esterl, W and Björck, Lars LU (1996) In Journal of Experimental Medicine 184(2). p.665-673
Abstract
Previous work has indicated a crucial role for the extracellular cysteine proteinase of Streptococcus pyogenes in the pathogenicity and virulence of this important human pathogen. Here we find that the purified streptococcal cysteine proteinase releases biologically active kinins from their purified precursor protein, H-kininogen, in vitro, and from kininogens present in the human plasma, ex vivo. Kinin liberation in the plasma is due to the direct action of the streptococcal proteinase on the kininogens, and does not involve the previous activation of plasma prekallikrein, the physiological plasma kininogenase. Judged from the amount of released plasma kinins the bacterial proteinase is highly efficient in its action. This is also the... (More)
Previous work has indicated a crucial role for the extracellular cysteine proteinase of Streptococcus pyogenes in the pathogenicity and virulence of this important human pathogen. Here we find that the purified streptococcal cysteine proteinase releases biologically active kinins from their purified precursor protein, H-kininogen, in vitro, and from kininogens present in the human plasma, ex vivo. Kinin liberation in the plasma is due to the direct action of the streptococcal proteinase on the kininogens, and does not involve the previous activation of plasma prekallikrein, the physiological plasma kininogenase. Judged from the amount of released plasma kinins the bacterial proteinase is highly efficient in its action. This is also the case in vivo. Injection of the purified cysteine proteinase into the peritoneal cavity of mice resulted in a progressive cleavage of plasma kininogens and the concomitant release of kinins over a period of 5 h. No kininogen degradation was seen in mice when the cysteine proteinase was inactivated by the specific inhibitor, Z-Leu-Val-Gly-CHN2, before administration. Intraperitoneal administration into mice of living S. pyogenes bacteria producing the cysteine proteinase induced a rapid breakdown of endogenous plasma kininogens and release of kinins. Kinins are hypotensive, they increase vascular permeability, contract smooth muscle, and induce fever and pain. The release of kinins by the cysteine proteinase of S. pyogenes could therefore represent an important and previously unknown virulence mechanism in S. pyogenes infections. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Experimental Medicine
volume
184
issue
2
pages
665 - 673
publisher
Rockefeller University Press
external identifiers
  • pmid:8760820
  • scopus:0029788388
ISSN
1540-9538
language
English
LU publication?
yes
id
428ba701-57ab-46e5-a941-60fe47c36b3a (old id 1109845)
alternative location
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2192748/
http://jem.rupress.org/content/184/2/665.long
date added to LUP
2008-07-24 08:31:17
date last changed
2017-08-06 04:32:18
@article{428ba701-57ab-46e5-a941-60fe47c36b3a,
  abstract     = {Previous work has indicated a crucial role for the extracellular cysteine proteinase of Streptococcus pyogenes in the pathogenicity and virulence of this important human pathogen. Here we find that the purified streptococcal cysteine proteinase releases biologically active kinins from their purified precursor protein, H-kininogen, in vitro, and from kininogens present in the human plasma, ex vivo. Kinin liberation in the plasma is due to the direct action of the streptococcal proteinase on the kininogens, and does not involve the previous activation of plasma prekallikrein, the physiological plasma kininogenase. Judged from the amount of released plasma kinins the bacterial proteinase is highly efficient in its action. This is also the case in vivo. Injection of the purified cysteine proteinase into the peritoneal cavity of mice resulted in a progressive cleavage of plasma kininogens and the concomitant release of kinins over a period of 5 h. No kininogen degradation was seen in mice when the cysteine proteinase was inactivated by the specific inhibitor, Z-Leu-Val-Gly-CHN2, before administration. Intraperitoneal administration into mice of living S. pyogenes bacteria producing the cysteine proteinase induced a rapid breakdown of endogenous plasma kininogens and release of kinins. Kinins are hypotensive, they increase vascular permeability, contract smooth muscle, and induce fever and pain. The release of kinins by the cysteine proteinase of S. pyogenes could therefore represent an important and previously unknown virulence mechanism in S. pyogenes infections.},
  author       = {Herwald, Heiko and Collin, Mattias and Muller-Esterl, W and Björck, Lars},
  issn         = {1540-9538},
  language     = {eng},
  number       = {2},
  pages        = {665--673},
  publisher    = {Rockefeller University Press},
  series       = {Journal of Experimental Medicine},
  title        = {Streptococcal cysteine proteinase releases kinins: a novel virulence mechanism},
  volume       = {184},
  year         = {1996},
}