Mechanical ventilation enhances Acinetobacter baumannii-induced lung injury through JNK pathways
Autor: | Tzyy Bin Tsay, Ching Mei Hsu, Lee Wei Chen, Wan Hsuan Chang |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Acinetobacter baumannii Male Alveolar macrophages Ventilator-Induced Lung Injury 030106 microbiology Nitric Oxide Synthase Type II Vascular Cell Adhesion Molecule-1 Inflammation Pharmacology Lung injury Nitric oxide 03 medical and health sciences chemistry.chemical_compound Diseases of the respiratory system Intensive care Macrophages Alveolar medicine Animals VCAM Mitogen-Activated Protein Kinase 8 Lung Cells Cultured Mice Knockout IL-6 medicine.diagnostic_test RC705-779 Chemistry Interleukin-6 Tumor Necrosis Factor-alpha Research Neutrophil Interleukin Pneumonia Ventilator-Associated respiratory system Respiration Artificial respiratory tract diseases Mice Inbred C57BL Disease Models Animal 030104 developmental biology Bronchoalveolar lavage BALF Neutrophil Infiltration Breathing Tumor necrosis factor alpha medicine.symptom Acinetobacter Infections Signal Transduction |
Zdroj: | Respiratory Research, Vol 22, Iss 1, Pp 1-14 (2021) Respiratory Research |
Popis: | Background 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). Methods 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. Results 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. Conclusion 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. |
Databáze: | OpenAIRE |
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