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

Autor: Tzyy Bin Tsay, Ching Mei Hsu, Lee Wei Chen, Wan Hsuan Chang
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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