Alpha-1 antitrypsin is markedly decreased following pulmonary F. tularensis challenge.
Alpha-1 antitrypsin is markedly decreased following pulmonary F. tularensis challenge.
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DOI：
10.3389/fcimb.2011.00020
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发表时间：
2011
影响因子：
5.7
通讯作者：
Arulanandam BP
中科院分区：
文献类型：
--
作者：
Chambers JP;Yu JJ;Jupelli M;Weintraub ST;Lopez-Ribot JL;Valdes JJ;Arulanandam BP
中性粒细胞在感染期间形成第一道防线，并且在此功能中不可或缺。中性粒细胞弹性蛋白酶是先天性免疫系统的关键效应分子，对革兰氏阴性菌、螺旋体和真菌具有强效抗微生物活性。然而，在细菌感染期间中性粒细胞弹性蛋白酶的释放必须被检查，否则其在细胞外环境中的释放将导致对周围组织的损伤。α-1抗胰蛋白酶是一种小的糖蛋白进化枝A丝氨酸丝氨酸蛋白酶抑制剂，并已被证明在细菌和病毒感染后在人类中增加。土拉热弗朗西斯菌是一种革兰氏阴性兼性胞内细菌，是土拉菌病的病原体。A型菌株毒性最强，感染剂量低至10个菌落形成单位，在未经治疗的肺炎土拉菌病病例中死亡率为30-60%。我们在这里报告显着减少这一主要抑制中性粒细胞弹性蛋白酶在血浆中的F。tularensisLVS和F.肺激发后土拉热菌（A型）SCHU S4感染的动物。与感染动物肺中肺泡水平的蛋白酶-抗蛋白酶功能失衡相关，在肺灌洗液中观察到弹性蛋白酶活性增加，伴有肺功能降低，即，肺弹性丧失，同时肺阻力增加。与F. tularensisLVS和F.土拉热菌（A型）SCHU S4肺激发并提出在急性期反应过程中上调血浆结合珠蛋白，观察到结合珠蛋白显著增加。这些数据表明，未经检查的中性粒细胞丝氨酸蛋白酶活性可能是由F。土拉菌靶向减少血浆α1-抗胰蛋白酶，促进肺组织损伤，促进该细菌在感染动物中的传播增加。
Neutrophils form the first line of defense during infection and are indispensable in this function. The neutrophil elastase is a key effector molecule of the innate immune system with potent antimicrobial activity against Gram-negative bacteria, spirochaetes, and fungi. However, the release of neutrophil elastase during bacterial infection must be checked otherwise its release in the extracellular milieu will result in damage to surrounding tissues. Alpha-1 antitrypsin is a small glycoprotein clade A serpine serine protease inhibitor and has been shown to increase in humans following bacterial and viral infection. Francisella tularensis is a Gram-negative facultative intracellular bacterium and the causative agent of tularemia. Type A strains are the most virulent with an infectious dose as low as 10 colony forming units and a mortality rate of 30–60% among untreated cases of pneumonic tularemia. We report here significant reduction of this major inhibitor of the neutrophil elastase in plasma of F. tularensis LVS and F. tularensis (type A) SCHU S4 infected animals following pulmonary challenge. Associated with an imbalance of protease–antiprotease function at the alveolar level in lungs of infected animals, increased elastase activity was observed in lung lavage fluids accompanied by decrease lung function, i.e., loss of lung elastance with concomitant increase of pulmonary hysteresivity. Consistent with a competent acute phase response following F. tularensis LVS and F. tularensis (type A) SCHU S4 pulmonary challenge and proposed up-regulation of plasma haptoglobin during the course of the acute phase reaction, haptoglobin was observed significantly increased. These data suggest that unchecked neutrophil serine protease activity may arise from F. tularensis targeted reduction of plasma α1-antitrysin promoting lung tissue damage facilitating increased dissemination of this bacterium in infected animals.
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影响因子：
3.1
作者：
Lindgren, H;Stenmark, S;Sjöstedt, A
通讯作者：
Sjöstedt, A
影响因子：
3.1
作者：
SCHRICKER, RL;HALL, WC;EIGELSBACH, HT
通讯作者：
EIGELSBACH, HT
影响因子：
3.8
作者：
Conlan, JW;KuoLee, R;Webb, A
通讯作者：
Webb, A
影响因子：
2.9
作者：
Bini, L;Magi, B;Pallini, V
通讯作者：
Pallini, V
影响因子：
5.8
作者：
KuoLee, Rhonda;Harris, Greg;Chen, Wangxue
通讯作者：
Chen, Wangxue