Rezaiguia S, Garat C, Delclaux C, Meignan M, Fleury J, Legrand P, Matthay M A, Jayr C
Department of Anesthesia, Institut National de la Santé et de la Recherche Médicale U 296, Hôpital Henri Mondor, Créteil, France.
J Clin Invest. 1997 Jan 15;99(2):325-35. doi: 10.1172/JCI119161.
To study the rate and regulation of alveolar fluid clearance in acute pneumonia, we created a model of Pseudomonas aeruginosa pneumonia in rats. To measure alveolar liquid and protein clearance, we instilled into the airspaces a 5% bovine albumin solution with 1.5 microCi of 125I-human albumin, 24 h after intratracheal instillation of bacteria. The concentration of unlabeled and labeled protein in the distal airspaces over 1 h was used as an index of net alveolar fluid clearance. Since there was histologic evidence of alveolar epithelial injury, several methods were used to measure alveolar fluid clearance, including the use of experiments in rats with blood flow and the use of experiments in rats without blood flow, so that movement across the epithelial barrier would be minimized in the latter group. The results with each method were identical. We found that P. aeruginosa pneumonia increased alveolar liquid clearance over 1 h by 48% in studies with blood flow, and by 43% in rats without blood flow, compared with respective controls (P < 0.05). In both studies, this increase was inhibited with amiloride. However, propranolol had no inhibitory effect, thus ruling out a catecholamine-dependent mechanism to explain the increase in alveolar fluid clearance. An antitumor necrosis factor-alpha neutralizing antibody, instilled into the lung 5 min before bacteria, prevented the increase in alveolar liquid clearance in rats with pneumonia (P < 0.05). Also, TNFalpha (5 microg) instilled in normal rats increased alveolar liquid clearance by 43% over 1 h compared with control rats (P < 0.05). In normal rats instilled with TNFalpha, propranolol had no inhibitory effect. In conclusion, gram-negative pneumonia markedly upregulates net alveolar epithelial fluid clearance, in part by a TNFalpha-dependent mechanism. This finding provides a novel mechanism for the upregulation of alveolar epithelial sodium and fluid transport from the distal airspaces of the lung.
为研究急性肺炎时肺泡液体清除率及其调节机制，我们建立了铜绿假单胞菌肺炎大鼠模型。为测量肺泡液体和蛋白质清除率，在气管内注入细菌24小时后，向肺泡腔内注入含1.5微居里125I -人白蛋白的5%牛白蛋白溶液。以1小时内远端肺泡腔中未标记和标记蛋白质的浓度作为肺泡液体净清除率的指标。由于存在肺泡上皮损伤的组织学证据，我们采用了多种方法测量肺泡液体清除率，包括对有血流的大鼠进行实验以及对无血流的大鼠进行实验，以使后一组中跨上皮屏障的移动最小化。每种方法的结果均相同。我们发现，与各自的对照组相比，在有血流的研究中，铜绿假单胞菌肺炎使1小时内肺泡液体清除率增加48%，在无血流的大鼠中增加43%（P < 0.05）。在两项研究中，这种增加均被氨氯吡咪抑制。然而，普萘洛尔没有抑制作用，从而排除了儿茶酚胺依赖性机制来解释肺泡液体清除率的增加。在细菌注入前5分钟向肺内注入抗肿瘤坏死因子-α中和抗体，可阻止肺炎大鼠肺泡液体清除率的增加（P < 0.05）。此外，与对照大鼠相比，向正常大鼠肺内注入肿瘤坏死因子-α（5微克）可使1小时内肺泡液体清除率增加43%（P < 0.05）。在注入肿瘤坏死因子-α的正常大鼠中，普萘洛尔没有抑制作用。总之，革兰氏阴性菌肺炎显著上调肺泡上皮液体净清除率，部分是通过肿瘤坏死因子-α依赖性机制。这一发现为肺远端肺泡腔中肺泡上皮钠和液体转运上调提供了一种新机制。
