Mechanical Ventilation Enhances Acinetobacter Baumannii-induced Lung Injury Through JNK Pathways

Overview

Journal Respir Res

Specialty Pulmonary Medicine

Date 2021 May 23

PMID 34022899

Citations 3

Authors

Tzyy-Bin Tsay

Wan-Hsuan Chang

Ching-Mei Hsu

Lee-Wei Chen

Affiliations

Soon will be listed here.

Abstract

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 × 10 colony-forming unit, CFU), or normal saline.

Results: 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.

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.

Citing Articles

Replicative Acinetobacter baumannii strains interfere with phagosomal maturation by modulating the vacuolar pH.

Distel J, Di Venanzio G, Mackel J, Rosen D, Feldman M PLoS Pathog. 2023; 19(6):e1011173.

PMID: 37294840 PMC: 10286980. DOI: 10.1371/journal.ppat.1011173.

Replicative strains interfere with phagosomal maturation by modulating the vacuolar pH.

Distel J, Di Venanzio G, Mackel J, Rosen D, Feldman M bioRxiv. 2023; .

PMID: 36778331 PMC: 9915592. DOI: 10.1101/2023.02.02.526753.

Neutrophil and Macrophage Response in Acinetobacter Baumannii Infection and Their Relationship to Lung Injury.

Liu Z, Xu W Front Cell Infect Microbiol. 2022; 12:890511.

PMID: 35873147 PMC: 9298752. DOI: 10.3389/fcimb.2022.890511.

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