Mechanical ventilation enhances Acinetobacter baumannii-induced lung injury through JNK pathways

Respiratory Research

Wan-Hsuan Chang¹  Ching-Mei Hsu¹  Lee-Wei Chen²  Tzyy-Bin Tsay³ 

[1]Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan

[2]Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan

[3]Department of Surgery, Kaohsiung Veterans General Hospital, 386, Ta-Chung 1st Road, Kaohsiung, Taiwan

[4]Institute of Emergency and Critical Care Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan

[5]Department of Surgery, Kaohsiung Armed Forces General Hospital Zuoying Branch, Kaohsiung, Taiwan

关键词: BALF;    VCAM;    IL-6;    Nitric oxide;    Neutrophil;    Alveolar macrophages;   

DOI  :  10.1186/s12931-021-01739-3

来源: Springer

【 摘 要 】

BackgroundPatients 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).MethodsC57BL/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 × 106 colony-forming unit, CFU), or normal saline.ResultsIntranasal instillation of 106 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.ConclusionA.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.

【 授权许可】

CC BY