Department of Surgery, Kaohsiung Armed Forces General Hospital Zuoying Branch, Kaohsiung, Taiwan.
Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan.
Respir Res. 2021 May 22;22(1):159. doi: 10.1186/s12931-021-01739-3.
Patients in intensive care units (ICUs) often received broad-spectrum antibiotic treatment and Acinetobacter baumannii (A.b.) and Pseudomonas aeruginosa (P.a.) were the most common pathogens causing ventilator-associated pneumonia (VAP). This study aimed to examine the effects and mechanism of mechanical ventilation (MV) on A.b.-induced lung injury and the involvement of alveolar macrophages (AMs).
C57BL/6 wild-type (WT) and c-Jun N-terminal kinase knockout (JNK1) mice received MV for 3 h at 2 days after nasal instillation of A.b., P.a. (1 × 10 colony-forming unit, CFU), or normal saline.
Intranasal instillation of 10 CFU A.b. in C57BL/6 mice induced a significant increase in total cells and protein levels in the bronchoalveolar lavage fluid (BALF) and neutrophil infiltration in the lungs. MV after A.b. instillation increases neutrophil infiltration, interleukin (IL)-6 and vascular cell adhesion molecule (VCAM) mRNA expression in the lungs and total cells, IL-6 levels, and nitrite levels in the BALF. The killing activity of AMs against A.b. was lower than against P.a. The diminished killing activity was parallel with decreased tumor necrosis factor-α production by AMs compared with A.b. Inducible nitric oxide synthase inhibitor, S-methylisothiourea, decreased the total cell number in BALF on mice receiving A.b. instillation and ventilation. Moreover, MV decreased the A.b. and P.a. killing activity of AMs. MV after A.b. instillation induced less total cells in the BALF and nitrite production in the serum of JNK1 mice than those of WT mice.
A.b. is potent in inducing neutrophil infiltration in the lungs and total protein in the BALF. MV enhances A.b.-induced lung injury through an increase in the expression of VCAM and IL-6 levels in the BALF and a decrease in the bacteria-killing activity of AMs. A lower inflammation level in JNK1 mice indicates that A.b.-induced VAP causes lung injury through JNK signaling pathway in the lungs.
重症监护病房（ICU）的患者经常接受广谱抗生素治疗，鲍曼不动杆菌（A.b.）和铜绿假单胞菌（P.a.）是引起呼吸机相关性肺炎（VAP）的最常见病原体。本研究旨在探讨机械通气（MV）对 A.b.诱导的肺损伤的影响及其肺泡巨噬细胞（AMs）的参与机制。
C57BL/6 野生型（WT）和 c-Jun N-末端激酶敲除（JNK1）小鼠在鼻内滴注 A.b.、P.a.（1×10 个菌落形成单位，CFU）或生理盐水后 2 天接受 3 小时 MV。
在 C57BL/6 小鼠中，鼻内滴注 10 CFU A.b.可导致支气管肺泡灌洗液（BALF）中总细胞和蛋白水平显著增加，并导致肺部中性粒细胞浸润。A.b.滴注后 MV 增加了肺部中性粒细胞浸润、白细胞介素（IL）-6 和血管细胞黏附分子（VCAM）mRNA 表达以及 BALF 中的总细胞数、IL-6 水平和亚硝酸盐水平。AMs 对 A.b.的杀伤活性低于对 P.a.的杀伤活性。与 A.b.相比，AMs 产生的肿瘤坏死因子-α减少，导致杀伤活性降低。诱导型一氧化氮合酶抑制剂 S-甲基异硫脲降低了接受 A.b.滴注和通气的小鼠 BALF 中的总细胞数。此外，MV 降低了 AMs 对 A.b.和 P.a.的杀伤活性。A.b.滴注后 MV 诱导的 JNK1 小鼠 BALF 中的总细胞数和血清中亚硝酸盐的产生低于 WT 小鼠。
A.b.可有效诱导肺部中性粒细胞浸润和 BALF 中的总蛋白。MV 通过增加 BALF 中 VCAM 和 IL-6 水平的表达以及降低 AMs 的细菌杀伤活性来增强 A.b.诱导的肺损伤。JNK1 小鼠的炎症水平较低表明，A.b.诱导的 VAP 通过肺部的 JNK 信号通路引起肺损伤。
