Terashima T, Matsubara H, Nakamura M, Sakamaki F, Waki Y, Soejima K, Tasaka S, Nakamura H, Sayama K, Ishizaka A, Kanazawa M
Department of Medicine, School of Medicine, Keio University, Tokyo, Japan.
Am J Respir Crit Care Med. 1996 May;153(5):1600-5. doi: 10.1164/ajrccm.153.5.8630608.
We investigated whether local bacterial instillation leads to lung injury in noninstilled lung regions and examined local and systemic cytokine accumulation. Rats were challenged by intrabroncheal instillation of Pseudomonas aeruginosa, 10(7) colony-forming units (CFU) (HD group, n = 11), 4 x 10(6) CFU (LD group, n = 10), or saline (control group, n = 12). 99mTc-labeled macroaggregated albumin was added to the P. aeruginosa or saline solution for later documentation of the instilled area. At 4 h the right lung, including instilled segment, and the left lung were sampled. Lung injury was assessed by lung tissue to plasma 125I-labeled albumin (T/P) and lung wet-dry (W/D) ratios. We measured plasma and bronchoalveolar lavage fluid (BALF) levels of tumor necrosis factor (TNF) and cytokine-induced neutrophil chemoattractant (CINC). HD bacterial instillation induced neutrophil recruitment and TNF and CINC elevation in BALF (p < 0.05) associated with increased T/P (p < 0.005) and W/D (p < 0.05) ratios in both instilled and the noninstilled lungs as compared with the saline-instilled and noninstilled controls. LD bacterial instillation induced neutrophil recruitment and TNF and CINC elevation only in the instilled lung (p < 0.05), and not in the noninstilled lung, and did not increase the T/P or W/D ratio. Plasma levels of TNF and CINC were increased in the HD, but not the LD, group when compared with the saline controls (p < 0.05). These data indicate that, when the dose is high enough to cause an excess inflammatory response, local bacterial instillation leads to neutrophil sequestration, lung injury, and cytokine elevation in the noninstilled lung associated with systemic cytokine release.
我们研究了局部细菌滴注是否会导致未滴注肺区域的肺损伤，并检测了局部和全身细胞因子的蓄积情况。通过经支气管内滴注铜绿假单胞菌对大鼠进行攻击，剂量分别为10⁷菌落形成单位（CFU）（高剂量组，n = 11）、4×10⁶CFU（低剂量组，n = 10）或生理盐水（对照组，n = 12）。将⁹⁹ᵐTc标记的大颗粒白蛋白加入铜绿假单胞菌或生理盐水溶液中，以便后续记录滴注区域。4小时后，对右肺（包括滴注节段）和左肺进行采样。通过肺组织与血浆中¹²⁵I标记白蛋白（T/P）以及肺湿干（W/D）比值评估肺损伤。我们检测了血浆和支气管肺泡灌洗液（BALF）中肿瘤坏死因子（TNF）和细胞因子诱导的中性粒细胞趋化因子（CINC）的水平。与滴注生理盐水和未滴注的对照组相比，高剂量细菌滴注诱导中性粒细胞募集以及BALF中TNF和CINC升高（p < 0.05），同时滴注肺和未滴注肺的T/P（p < 0.005）和W/D（p < 0.05）比值增加。低剂量细菌滴注仅在滴注肺中诱导中性粒细胞募集以及TNF和CINC升高（p < 0.05），在未滴注肺中未出现，且未增加T/P或W/D比值。与生理盐水对照组相比，高剂量组血浆中TNF和CINC水平升高，而低剂量组未升高（p < 0.05）。这些数据表明，当剂量高到足以引起过度炎症反应时，局部细菌滴注会导致中性粒细胞滞留、肺损伤以及未滴注肺中细胞因子升高，并伴有全身细胞因子释放。
