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- Title
Mechanical ventilation enhances Acinetobacter baumannii-induced lung injury through JNK pathways.
- Authors
Tsay, Tzyy-Bin; Chang, Wan-Hsuan; Hsu, Ching-Mei; Chen, Lee-Wei
- Abstract
<bold>Background: </bold>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).<bold>Methods: </bold>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 × 106 colony-forming unit, CFU), or normal saline.<bold>Results: </bold>Intranasal 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.<bold>Conclusion: </bold>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.
- Subjects
VENTILATOR-associated pneumonia; CELL adhesion molecules; LUNG injuries; ARTIFICIAL respiration; NITRIC-oxide synthases; INTENSIVE care patients; NITRIC oxide; LUNG microbiology; INTERLEUKINS; BIOLOGICAL models; ACINETOBACTER infections; CELL culture; LUNGS; MECHANICAL ventilators; ANIMAL experimentation; MACROPHAGES; CELLULAR signal transduction; GRAM-negative aerobic bacteria; TRANSFERASES; TUMOR necrosis factors; IMMUNITY; OXIDOREDUCTASES; ANTIGENS; ANIMALS; MICE
- Publication
Respiratory Research, 2021, Vol 22, Issue 1, p1
- ISSN
1465-9921
- Publication type
journal article
- DOI
10.1186/s12931-021-01739-3