Kudoh I, Wiener-Kronish J P, Hashimoto S, Pittet J F, Frank D
Department of Anesthesia, University of California at San Francisco 94143-0130.
Am J Physiol. 1994 Nov;267(5 Pt 1):L551-6. doi: 10.1152/ajplung.1994.267.5.L551.
To determine whether exoenzyme S plays a role in alveolar epithelial injury, two parental strains of Pseudomonas aeruginosa, PAK and PA103, were tested that produced large quantities of exoenzyme S. Strains PAK and PA103 differ in the form of exoenzyme S they produce. Strain PAK produces a 53-kDa protein that does not possess ADP-ribosyltransferase activity and large quantities of a 49-kDa protein that expresses ADP-ribosyltransferase activity. Strain PA103 produces the 53-kDa protein and low amounts of exoenzyme S activity. A quantitative experimental protocol was used to measure the protein permeability of the alveolar epithelium and the dissemination of the bacteria to the pleural space and circulation. The results indicate that instillation of PAK and PA103 resulted in significant lung injury. Control experiments utilizing isogenic, exoenzyme S-deficient, regulatory mutants in the infection model reduced the lung injury and the dissemination of instilled bacteria. Taken together these results suggest that alveolar epithelial injury correlated with the production of the 53-kDa form of exoenzyme S or other coordinately regulated factors.
为了确定外毒素S是否在肺泡上皮损伤中起作用,对两种能产生大量外毒素S的铜绿假单胞菌亲本菌株PAK和PA103进行了测试。PAK和PA103菌株产生的外毒素S形式不同。PAK菌株产生一种不具有ADP-核糖基转移酶活性的53 kDa蛋白以及大量具有ADP-核糖基转移酶活性的49 kDa蛋白。PA103菌株产生53 kDa蛋白且外毒素S活性较低。采用定量实验方案来测量肺泡上皮的蛋白质通透性以及细菌向胸膜腔和循环系统的扩散情况。结果表明,滴注PAK和PA103会导致严重的肺损伤。在感染模型中利用同基因、外毒素S缺陷型调控突变体进行的对照实验减轻了肺损伤以及滴注细菌的扩散。综合这些结果表明,肺泡上皮损伤与53 kDa形式的外毒素S或其他协同调节因子的产生有关。