Local Pseudomonas instillation induces contralateral lung injury and plasma cytokines

Local Pseudomonas instillation induces contralateral lung injury and plasma cytokines
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DOI:
10.1164/ajrccm.153.5.8630608
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发表时间:
1996-05-01
影响因子:
24.7
通讯作者:
Kanazawa, M
Kanazawa, M
中科院分区:
医学1区
文献类型:
--
作者:
Terashima, T;Matsubara, H;Kanazawa, M

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我们研究了局部细菌灌注是否会导致非灌注肺区域的肺损伤,并检查了局部和全身细胞因子的积累。通过支气管内滴注铜绿假单胞菌、10(7)个菌落形成单位(CFU)(HD组,n = 11)、4 × 10(6)个CFU(LD组,n = 10)或生理盐水(对照组,n = 12)激发大鼠。将Tc-99 m标记的大颗粒聚集白蛋白加入到铜绿假单胞菌或盐水溶液中,用于随后记录滴注区域。在4 h时,对右肺(包括滴注段)和左肺取样。肺组织/血浆I-125标记白蛋白(T/P)和肺湿/干(W/D)比值评估肺损伤。我们测量了血浆和支气管肺泡灌洗液(BALF)中肿瘤坏死因子(TNF)和苦参碱诱导的中性粒细胞趋化因子(CINC)的水平。与盐水灌注和非灌注对照组相比,HD细菌灌注诱导BALF中中性粒细胞募集和TNF和CINC升高(p <0.05),与灌注和非灌注肺中T/P(p < 0.005)和W/D(p < 0.05)比值增加相关。LD细菌灌注仅在灌注肺中诱导中性粒细胞募集和TNF和CINC升高(p < 0.05),而在非灌注肺中不诱导,并且不增加T/P或W/D比值。与生理盐水对照组相比,HD组血浆TNF和CINC水平升高,但LD组无此变化(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,局部细菌滴注导致中性粒细胞隔离、肺损伤和与全身细胞因子释放相关的非滴注肺中细胞因子升高。
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). Tc-99m-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 I-125-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.