Specific C-terminal cleavage and inactivation of interleukin-8 by invasive disease isolates of Streptococcus pyogenes
Specific C-terminal cleavage and inactivation of interleukin-8 by invasive disease isolates of Streptococcus pyogenes
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DOI：
10.1086/432485
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发表时间：
2005-09-01
影响因子：
6.4
通讯作者：
Sriskandan, S
中科院分区：
文献类型：
--
作者：
Edwards, RJ;Taylor, GW;Sriskandan, S
化脓性链球菌引起的致死性坏死性筋膜炎的特征是感染部位中性粒细胞缺乏。白细胞介素（IL）-8在中性粒细胞的迁移和活化中起重要作用。化脓血分离株S.化脓性链球菌比咽喉分离物更能降解人IL-8。IL-8的降解是IL-8 C-末端α螺旋内（59）谷氨酰胺和（60）精氨酸之间单一特异性切割的结果。裂解的IL-8减少中性粒细胞活化和迁移。在坏死性筋膜炎分离株的部分纯化的上清液中发现IL-8裂解活性，该活性与含有S.化脓性链球菌细胞膜蛋白酶（SpyCEP）。IL-8裂解活性对应于上清液中SpyCEP的存在。S.化脓性链球菌代表了一种前所未有的免疫逃避机制，有效地阻止了IL-8 C-末端介导的内皮易位和随后的中性粒细胞募集。
Lethal necrotizing fasciitis caused by Streptococcus pyogenes is characterized by a paucity of neutrophils at the site of infection. Interleukin (IL)-8, which is important for neutrophil transmigration and activation, can be degraded by S. pyogenes. Blood isolates of S. pyogenes were better able to degrade human IL-8 than throat isolates. Degradation of IL-8 was the result of a single specific cleavage between (59)glutamine and (60)arginine within the IL-8 C-terminal a helix. Cleaved IL-8 reduced neutrophil activation and migration. IL-8-cleaving activity was found in partially purified supernatant of a necrotizing fasciitis isolate, and this activity was associated with an similar to 150-kDa fraction containing S. pyogenes cell envelope proteinase (SpyCEP). IL-8-cleaving activity corresponded with the presence of SpyCEP in the supernatant. Cleavage of IL-8 by S. pyogenes represents an unprecedented mechanism of immune evasion, effectively preventing IL-8 C-terminus-mediated endothelial translocation and subsequent recruitment of neutrophils.