Wiener-Kronish J P, Sakuma T, Kudoh I, Pittet J F, Frank D, Dobbs L, Vasil M L, Matthay M A
Department of Anesthesia, University of California at San Francisco 94143-0130.
J Appl Physiol (1985). 1993 Oct;75(4):1661-9. doi: 10.1152/jappl.1993.75.4.1661.
We developed an experimental model of acute Pseudomonas aeruginosa pneumonia in anesthetized ventilated rabbits to determine whether bacterial-induced injury to the alveolar epithelium would occur and the effect of the injury on the pleural space. Dose-response studies established that 10(9) colony-forming units of P. aeruginosa (wild-type strain, PAO-1) were required to injure the epithelial barrier and to cause pleural empyema with exudative pleural effusions that contained both the instilled alveolar protein tracer and P. aeruginosa. We explored the mechanisms of P. aeruginosa-induced lung and pleural injury by using three isogenic bacterial strains to compare several extracellular virulence products. PAO-S21, which carries an insertion mutation in a regulatory gene that prevents the production of exoenzyme S, resulted in no lung or pleural injury. PAO-R1, which carries a deletion in a regulatory gene that controls the production of elastase and alkaline protease, caused the same degree of lung and pleural injury as PAO-1 did. Instillation of PLC-SRN, which has both structural genes encoding phospholipase C activity deleted, resulted in a moderate reduction in alveolar epithelial injury. Although other products may be involved, exoenzyme S and phospholipase C are important in mediating injury to the alveolar epithelial barrier in acute P. aeruginosa pneumonia in rabbits.
我们建立了麻醉通气兔急性铜绿假单胞菌肺炎的实验模型，以确定细菌是否会导致肺泡上皮损伤以及该损伤对胸膜腔的影响。剂量反应研究表明，需要10⁹个铜绿假单胞菌（野生型菌株，PAO-1）菌落形成单位才能损伤上皮屏障并导致胸膜积脓，伴有渗出性胸腔积液，其中既含有注入的肺泡蛋白示踪剂，也含有铜绿假单胞菌。我们使用三种同基因菌株比较几种细胞外毒力产物，以探究铜绿假单胞菌诱导的肺和胸膜损伤机制。PAO-S21在一个调控基因中携带插入突变，阻止外毒素S的产生，未导致肺或胸膜损伤。PAO-R1在一个控制弹性蛋白酶和碱性蛋白酶产生的调控基因中存在缺失，导致的肺和胸膜损伤程度与PAO-1相同。注入编码磷脂酶C活性的两个结构基因均缺失的PLC-SRN，可使肺泡上皮损伤适度减轻。尽管可能涉及其他产物，但外毒素S和磷脂酶C在介导兔急性铜绿假单胞菌肺炎中肺泡上皮屏障损伤方面很重要。
