Tasaka S, Ishizaka A, Sayama K, Sakamaki F, Nakamura H, Terashima T, Waki Y, Soejima K, Nakamura M, Matsubara H, Fujishima S, Kanazawa M
Department of Medicine, School of Medicine, Keio University, Tokyo, Japan.
Am J Respir Crit Care Med. 1996 Mar;153(3):1047-55. doi: 10.1164/ajrccm.153.3.8630544.
Corynebacterium parvum (CP) is known to increase susceptibility to endotoxin, which is associated with increased production of tumor necrosis factor (TNF). We investigated the effect of CP-priming on the pathogenesis of acute lung injury caused by intratracheal Escherichia coli endotoxin (lipopolysaccharide [LPS]). Guinea pigs were divided into four groups: (1) control (n=6), (2) CP-alone (n=6), (3) LPS-alone (n=6) and (4) CP + LPS (n=6). A CP dose of 4 mg/kg was injected intraperitoneally 7 d before the study. Animals were observed for 4 h after intratracheal administration of 0.02 mg/kg of LPS. The lung wet-to-dry weight ratio (W/D), [125I] albumin concentration ratio of lung tissue to plasma (T/P) and of bronchoalveolar lavage (BAL) fluid to plasma (B/P) and differential cell count in BAL fluid were examined. In the LPS-alone group, neither excess lung water nor increased albumin leakage was observed. The CP + LPS group showed increased lung water and albumin leakage as compared with the other three groups (p<0.05). We also observed increased cell counts in BAL fluid (p<0.05), in the CP + LPS group. The spleen weight was increased in guinea pigs pretreated with CP, indicating reticuloendothelial system (RES) activation. In the CP + LPS group, the TNF level was increased in both plasma and BAL fluid. We conclude that pretreatment with CP enhances LPS-induced acute lung injury in parallel with increasing TNF production, which suggests that the activation of mononuclear phagocytes contributes to increased susceptibility to intratracheal endotoxin in guinea pigs.
已知短小棒状杆菌（CP）会增加对内毒素的易感性，这与肿瘤坏死因子（TNF）产生增加有关。我们研究了CP预处理对气管内注射大肠杆菌内毒素（脂多糖[LPS]）所致急性肺损伤发病机制的影响。将豚鼠分为四组：（1）对照组（n = 6），（2）单独CP组（n = 6），（3）单独LPS组（n = 6）和（4）CP + LPS组（n = 6）。在研究前7天腹腔注射4 mg/kg的CP剂量。气管内给予0.02 mg/kg LPS后观察动物4小时。检测肺湿重与干重比（W/D）、肺组织与血浆的[125I]白蛋白浓度比（T/P）、支气管肺泡灌洗（BAL）液与血浆的浓度比（B/P）以及BAL液中的细胞分类计数。在单独LPS组中，未观察到肺水过多或白蛋白渗漏增加。与其他三组相比，CP + LPS组肺水和白蛋白渗漏增加（p<0.05）。我们还观察到CP + LPS组BAL液中的细胞计数增加（p<0.05）。用CP预处理的豚鼠脾脏重量增加，表明网状内皮系统（RES）激活。在CP + LPS组中，血浆和BAL液中的TNF水平均升高。我们得出结论，CP预处理会增强LPS诱导的急性肺损伤，同时增加TNF的产生，这表明单核吞噬细胞的激活导致豚鼠对气管内毒素的易感性增加。
