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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1109845
- author
- Herwald, Heiko
LU
; Collin, Mattias
LU
; Muller-Esterl, W
and Björck, Lars
LU
- organization
- publishing date
- 1996
- 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
- 2016-04-01 16:16:51
- date last changed
- 2022-03-22 17:32:59
@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}},
url = {{https://lup.lub.lu.se/search/files/28467658/je1842665.pdf}},
volume = {{184}},
year = {{1996}},
}