Abstract
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.
Highlights
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 ventilatorassociated pneumonia (VAP)
mechanical ventilation (MV) enhances A.b.‐induced neutrophil infiltration in the lungs To investigate the effects of MV on A.b.-induced neutrophil infiltration in the lungs, pulmonary myeloperoxidase (MPO) activity was examined in different groups
MV enhances A.b.‐induced interleukin (IL)‐6 expression and alveolar wall thickening in the lungs To examine the effects of MV on A.b.- or P.a.-induced inflammatory cytokine expression in the lungs, expression of tumor necrosis factor (TNF)-α, IL-1β, and IL-6 mRNA in the lungs were examined in different groups
Summary
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 ventilatorassociated pneumonia (VAP). Patients hospitalized in intensive care units (ICUs) often received broad spectrum antibiotic treatment which may lead to frequent isolation of A.b. strain from patients [2, 3]. Recruitment of neutrophils into the lungs is critical for initiating an efficient host defense against A.b. infection [6]. Macrophages may be involved in early host defense against A.b. infection through a more efficient phagocytosis and killing of A.b., limiting initial pathogen replication and secretion of pro-inflammatory cytokines/chemokines for the rapid recruitment of other innate immune cells such as neutrophils [7]. The management of VAP caused by drugresistant A.b. is still a challenge
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