Streptococcal cysteine proteinase releases kinins: A novel virulence mechanism

被引:143
作者
Herwald, H [1 ]
Collin, M [1 ]
MullerEsterl, W [1 ]
Bjorck, L [1 ]
机构
[1] UNIV MAINZ, INST PHYSIOL CHEM & PATHOBIOCHEM, D-55099 MAINZ, GERMANY
关键词
D O I
10.1084/jem.184.2.665
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 man plasma, ex vivo. Kinin liberation in tf lr 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 ill its action. This is also the case in vivo. Injection of the purified cysteine proteinase into the peritoneal cavity oi 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 ill 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.
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页码:665 / 673
页数:9
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