Streptococcal cysteine proteinase releases kinins: A novel virulence mechanism
Streptococcal cysteine proteinase releases kinins: A novel virulence mechanism
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DOI：
10.1084/jem.184.2.665
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发表时间：
1996-08-01
影响因子：
15.3
通讯作者：
Bjorck, L
中科院分区：
文献类型：
--
作者：
Herwald, H;Collin, M;Bjorck, L
以往的工作表明，化脓性链球菌的胞外半胱氨酸蛋白酶在这种重要的人类病原体的致病性和毒力中起着至关重要的作用。在这里，我们发现，纯化的链球菌半胱氨酸蛋白酶释放生物活性激肽从其纯化的前体蛋白，H-激肽原，在体外，和从激肽原人血浆，离体。tf lr血浆中的激肽释放是由于链球菌蛋白酶对激肽原的直接作用，而不涉及血浆前激肽释放酶（生理性血浆激肽原酶）的预先激活。从释放的血浆激肽的量来判断，细菌蛋白酶的作用是高效的。在体内也是如此。将纯化的半胱氨酸蛋白酶注入小鼠腹腔，在5小时内，血浆激肽原发生进行性裂解，并伴随着激肽的释放。用特异性抑制剂Z-Leu-Val-Gly-CHN_2灭活半胱氨酸蛋白酶后，小鼠体内未见激肽原降解。小鼠腹腔注射活S.产生半胱氨酸蛋白酶的化脓性细菌诱导内源性血浆激肽原的快速分解和激肽的释放。激肽是扩张性的，它们增加血管通透性，收缩平滑肌，并引起发热和疼痛。S.因此，化脓性链球菌可能代表了一种重要的和以前未知的毒力机制。化脓性感染
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.