Pittet J F, Matthay M A, Pier G, Grady M, Wiener-Kronish J P
Cardiovascular Research Institute, University of California, San Francisco 94143.
J Clin Invest. 1993 Sep;92(3):1221-8. doi: 10.1172/JCI116693.
The overall objective of these studies was to determine whether IgG antibody to Pseudomonas aeruginosa would modify the acute lung and pleural injury that developed over 24 h after the instillation of 10(10) live P. aeruginosa into the distal airspaces of one lung in unanesthetized sheep. Using a quantitative experimental model to measure protein permeability across the alveolar epithelial, lung endothelial, and pleural mesothelial barriers, the effect of IgG antibody to P. aeruginosa was examined under four different experimental conditions. First, the effect of IgG antibody to P. aeruginosa in the circulation was examined by instilling 10(10) live P. aeruginosa in 5% ovine albumin in sheep that had been vaccinated. Under these conditions, the presence of circulating IgG antibody to P. aeruginosa reduced lung endothelial injury but did not modify the lung epithelial or pleural injury caused by intraalveolar P. aeruginosa. Therefore, the second experimental protocol determined the effect of instilling immune serum from a sheep that had been vaccinated so that IgG antibody to P. aeruginosa was present in both the circulation and in the airspaces along with instillation of live bacteria. Under these conditions, injury to the lung endothelium, alveolar epithelium, and pleural space was completely prevented. Therefore, the third protocol examined the protective effect of instillation of IgG antibody to P. aeruginosa in the airspaces concurrent with the live bacteria. Interestingly, intraalveolar IgG antibody to P. aeruginosa prevented all evidence of lung epithelial and pleural injury, and this effect was associated with a marked decrease in the number of viable bacteria in the lung after 24 h. Therefore, the fourth protocol examined the prophylactic effect of instillation of the specific IgG antibody to P. aeruginosa 24 h before instillation of the bacteria. With this prophylactic regimen, epithelial, endothelial, and pleural injury were prevented, and there was a significant decrease in the number of bacteria recovered from the lung. Thus, delivery of IgG antibody to P. aeruginosa the distal airspaces of the lung alone may provide a novel therapeutic approach to preventing acute pulmonary infection caused by P. aeruginosa.
这些研究的总体目标是确定抗铜绿假单胞菌IgG抗体是否会改变在未麻醉绵羊的一侧肺远端气腔中注入10¹⁰ 活铜绿假单胞菌后24小时内发生的急性肺和胸膜损伤。使用定量实验模型来测量蛋白质穿过肺泡上皮、肺内皮和胸膜间皮屏障的通透性，在四种不同实验条件下检测了抗铜绿假单胞菌IgG抗体的作用。首先，通过在已接种疫苗的绵羊中注入含10¹⁰ 活铜绿假单胞菌的5%绵羊白蛋白来检测循环中抗铜绿假单胞菌IgG抗体的作用。在这些条件下，循环中抗铜绿假单胞菌IgG抗体的存在减轻了肺内皮损伤，但未改变肺泡内铜绿假单胞菌引起的肺上皮或胸膜损伤。因此，第二个实验方案确定了注入来自已接种疫苗绵羊的免疫血清的作用，这样在注入活细菌时，循环中和气腔中都存在抗铜绿假单胞菌IgG抗体。在这些条件下，肺内皮、肺泡上皮和胸膜腔的损伤被完全预防。因此，第三个方案检测了在注入活细菌的同时在气腔中注入抗铜绿假单胞菌IgG抗体的保护作用。有趣的是，肺泡内抗铜绿假单胞菌IgG抗体预防了所有肺上皮和胸膜损伤的迹象，并且这种作用与24小时后肺内活菌数量的显著减少有关。因此，第四个方案检测了在注入细菌前24小时注入抗铜绿假单胞菌特异性IgG抗体的预防作用。采用这种预防方案，上皮、内皮和胸膜损伤得到了预防，并且从肺中回收的细菌数量显著减少。因此，仅将抗铜绿假单胞菌IgG抗体递送至肺的远端气腔可能为预防铜绿假单胞菌引起的急性肺部感染提供一种新的治疗方法。
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