Macrophage Activation in Stellate Ganglia Contributes to Lung Injury‐Induced Arrhythmogenesis in Male Rats

Aim: Thus far, the anti-inflammatory effect of vanillin in acute lung injury (ALI) has not been studied. This study aimed to investigate the effect of vanillin in lipopolysaccharide (LPS)-induced ALI. Results & methodology: Our study detected the anti-inflammatory effects of vanillin by ELISA and western blot, respectively. Pretreatment of mice with vanillin significantly attenuated LPS-stimulated lung histopathological changes, myeloperoxidase activity and expression levels of proinflammatory cytokines by inhibiting the phosphorylation activities of ERK1/2, p38, AKT and NF-κB p65. In addition, vanillin inhibited LPS-induced TNF-α and IL-6 expression in RAW264.7 cells via ERK1/2, p38 and NF-κB signaling. Conclusion: Vanillin can inhibit macrophage activation and lung inflammation, which suggests new insights for clinical treatment of ALI.

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Huangkui Capsule Attenuates Lipopolysaccharide-Induced Acute Lung Injury and Macrophage Activation by Suppressing Inflammation and Oxidative Stress in Mice

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/6626483 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Jinfang Deng ◽

Zhenpeng He ◽

Xiuru Li ◽

Wei Chen ◽

Ziwen Yu ◽

...

Keyword(s):

Oxidative Stress ◽

Acute Lung Injury ◽

Lung Injury ◽

Macrophage Activation ◽

Neutrophil Infiltration ◽

Raw 264.7 Cells ◽

Raw 264.7 ◽

Myeloperoxidase Activity ◽

Tnf Α ◽

And Oxidative Stress

Background. Huangkui capsule (HKC) comprises the total flavonoid extract of flowers of Abelmoschus manihot (L.) Medicus. This study aimed to explore the effects of HKC on lipopolysaccharide- (LPS-) induced acute lung injury (ALI) in mice and LPS-stimulated RAW 264.7 cells. Methods. Enzyme-linked immunosorbent assay, histopathology, spectrophotometry, and quantitative real-time polymerase chain reaction were used for the assessments. Statistical analysis was performed using a one-way analysis of variance. Results. LPS significantly increased lung inflammation, neutrophil infiltration, and oxidative stress and downregulated lung miR-451 expression. Treatment with HKC dramatically attenuated the lung wet/dry weight ratio, reduced the total cell count in the bronchoalveolar lavage fluid (BALF), and inhibited myeloperoxidase activity in the lung tissues 24 h after LPS challenge. Histopathological analysis demonstrated that HKC attenuated LPS-induced tissue oedema and neutrophil infiltration in the lung tissues. Additionally, the concentrations of tumour necrosis factor- (TNF-) α and interleukin- (IL-) 6 in BALF and IL-6 in the plasma reduced after HKC administration. Moreover, HKC could enhance glutathione peroxidase and catalase activities and upregulate the expression of miR-451 in the lung tissues. In vitro experiments revealed that HKC inhibited the production of nitric oxide, TNF-α, and IL-6 in LPS-induced RAW 264.7 cells and mouse primary peritoneal macrophages. Additionally, HKC downregulated LPS-induced transcription of TNF-α and IL-6 in RAW 264.7 cells. Conclusions. These findings suggest that HKC has anti-inflammatory and antioxidative effects that may protect mice against LPS-induced ALI and macrophage activation.

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Abstract P2004: Neural Inflammation in Stellate Ganglia Mediates Lung Injury-Induced Arrhythmogenesis

Hypertension ◽

10.1161/hyp.74.suppl_1.p2004 ◽

2019 ◽

Vol 74 (Suppl_1) ◽

Author(s):

Ryan Adam ◽

Lie Gao ◽

Juan Hong ◽

Irving H Zucker ◽

Steven J Lisco ◽

...

Keyword(s):

Lung Injury ◽

Stellate Ganglia

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Ventilator-Induced Lung Injury Is Associated with Neutrophil Infiltration, Macrophage Activation, and TGF-β1 mRNA Upregulation in Rat Lungs

Anesthesia & Analgesia ◽

10.1097/00000539-200102000-00029 ◽

2001 ◽

Vol 92 (2) ◽

pp. 428-436 ◽

Cited By ~ 9

Author(s):

Hideaki Imanaka ◽

Motomu Shimaoka ◽

Nariaki Matsuura ◽

Masaji Nishimura ◽

Noriyuki Ohta ◽

...

Keyword(s):

Lung Injury ◽

Macrophage Activation ◽

Neutrophil Infiltration ◽

Ventilator Induced Lung Injury ◽

Rat Lungs ◽

Tgf Β1

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СУБМІКРОСКОПІЧНІ ЗМІНИ КОМПОНЕНТІВ АЕРОГЕМАТИЧНОГО БАР’ЄРУ РЕСПІРАТОРНОГО ВІДДІЛУ ЛЕГЕНЬ ЩУРІВ У РАННІ ТЕРМІНИ ПІСЛЯ ГОСТРОГО УРАЖЕННЯ ХЛОРИДНОЮ КИСЛОТОЮ

Вісник наукових досліджень ◽

10.11603/2415-8798.2018.2.9154 ◽

2018 ◽

Author(s):

V. O. Beskyy ◽

Z. M. Nebesna ◽

M. I. Marushchak ◽

L. A. Hryshchuk

Keyword(s):

Acute Lung Injury ◽

Hydrochloric Acid ◽

Lung Injury ◽

Early Period ◽

Alveolar Epithelium ◽

Male Rats ◽

Control Group ◽

Ultrastructural Organization ◽

Type I ◽

White Rats

Submicroscopic studies of the respiratory part of the lungs after 2 and 6 hours after the experimental acute lung injury with hydrochloric acid established adaptive-compensatory and destructive changes in the components of the air-blood barrier.The aim of the study – to learn submicroscopic changes in the components of the air-blood barrier of the lungs in the early period after acute lung injury.Materials and Methods. The experiments were carried out on 30 white mature non-linear male rats weighing 200–220 g. The animals were divided into 3 groups: 1 – control group, 2 – hydrochloric acid damage after 2 hours, 3 – hydrochloric acid damage after 6 hour.Results and Discussion. In an experiment on mature white rats, a study was made of the submicroscopic state of the components of the air-blood barrier in the early periods after acute lung injury. It has been established that adaptive-compensatory and initial destructive changes of the alveolar epithelium and the walls of the hemocapillary take place at 2 o'clock in the experiment. The cytoplasm of respiratory epitheliocytes during this period of the experiment was focal-edematous and enlightened, organelles were destructively altered. For alveolocytes of type I, there was a significant swelling and clarification of the cytoplasm. During this period of the experiment, an increased number of actively phagocytizing macrophages appeared, which acquired a rounded shape, clearly contoured membranes of the cariolema, their invaginations were determined, and in the karyoplasm euchromatin predominated. In alveolocytes of type II, after 6 hours, the progression of destructive changes was established. For which there were peculiarity hypertrophied nuclei with deep invagination of the cariolema, in which there were few nuclear pores, locally expanded perinuclear space. In the edematous cytoplasm, organelles were found to be destructively altered.Conclusions. Acute damage to the lungs leads to a disruption of the ultrastructural organization of the air-blood barrier. Established adaptive-compensatory processes and signs of destructive changes in the alveolar epithelium and the walls of hemocapillaries, which leads to deterioration of gas-exchange processes in the lungs.

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Mesenchymal Stem Cells Attenuate Acute Lung Injury in Mice Partly by Suppressing Alveolar Macrophage Activation in a PGE2-dependent Manner

10.21203/rs.3.rs-664786/v1 ◽

2021 ◽

Author(s):

Gaojian Wang ◽

Yaping Zhang ◽

Nianqiang Hu ◽

Qinxue Liu ◽

Fengjie Ma ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Alveolar Macrophage ◽

Alveolar Macrophages ◽

Macrophage Activation ◽

Rna Seq ◽

Ep4 Receptor ◽

Pge2 Receptor ◽

Cox2 Inhibitor

Abstract Background: Mesenchymal stem cell have shown therapeutic effect on acute lung injury, MSC could be activated when added to inflammatory environment and in turn suppress inflammation, yet the mechanism is complex and not understood. Methods: To determine the effect of MSC on ALI and alveolar macrophage activation, MSCs were administered to ALI mice and co-cultured with activated MH-S cells (alveolar macrophage cell line). To find the genes critical for MSC’s immunosuppressive effects, rest and activated MSCs induced by inflammatory MH-S cells were harvested for RNA-seq. To prove that PGE2 participates in the immunosuppressive effects of MSC, COX2 inhibitor and PGE2 receptor antagonist were added to the co-culture system and administrated to ALI mice. Results: The intratracheal administration of MSCs attenuated ALI and suppressed alveolar macrophages activation in vivo, the activation of MH-S cells was also significantly reduced after co-culturing with MSCs in vitro. The RNA-seq data of rest and activated MSCs suggested that the Ptgs2 gene may play an important role in MSC exerting immunosuppressive effects. Correspondingly, we found that the COX2 protein and PGE2 released by activated MSCs were increased dramatically after co-culturing with MH-S. The use of COX2 inhibitor NS-398 restrained the secretion of PGE2 and reversed the suppressive effect on macrophages activation of MSCs in vitro. Furthermore, GW627368X, a selective antagonist of PGE2 receptor (EP4 receptor), also reversed the inhibitory effects of MSCs on alveolar macrophages and their protective effects on ALI mice.Conclusions: MSC attenuate ALI partly through suppressing alveolar macrophage activation via PGE2 binding to EP4 receptor.

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Effect of Recombinant Human Thrombomodulin on Ventilator-Induced Lung Injury in Septic Rats

10.21203/rs.3.rs-139841/v1 ◽

2021 ◽

Author(s):

Yoshiaki Iwashita ◽

Zhang Erquan ◽

Hirofumi Sawada ◽

Masako Kawai ◽

Junko Maruyama ◽

...

Keyword(s):

Lung Injury ◽

Tidal Volume ◽

Cecal Ligation ◽

Male Rats ◽

High Tidal Volume ◽

Mrna Levels ◽

Protein Levels ◽

Ventilator Induced Lung Injury ◽

Tidal Ventilation ◽

Recombinant Thrombomodulin

Abstract Background: High tidal ventilation with inflammation causes ventilator-induced lung injury (VILI). We previously found that recombinant thrombomodulin (rTM) has a protective effect regarding non-septic VILI caused by high-tidal-volume (HV) ventilation with high oxygen levels. This study aimed to investigate the preventive effect of rTM on VILI caused by sepsis and HV ventilation. Methods: A total of 46 adult male rats were subcutaneously administered either 3mg/kg of rTM or saline. Twelve hours later, the rats were underwent cecal ligation and puncture (CLP). At 2 h after this procedure, the rats were placed on a ventilator set at either low tidal volume [(LV) 6 ml/kg] or high tidal volume (HV 35 ml/kg) ventilation for another 2 h. Results: After 2 h of mechanical ventilation, the PaO2 was significantly lower and BALF protein was significantly higher in HV rats than in LV rats. The rTM did not improve oxygenation or BALF protein levels. Also in HV rats, lung tissue interleukin-6 and monocyte chemotactic protein-1 mRNA levels were significantly higher in the rTM-treated rats.Conclusion: rTM does not improve oxygenation in a non-DIC, CLP-pretreated, high-tidal-ventilation rat model.

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Geranylgeranyl diphosphate synthase deficiency hyperactivates macrophages and aggravates lipopolysaccharide-induced acute lung injury

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00281.2020 ◽

2021 ◽

Author(s):

Jiajia Jin ◽

Hong Qian ◽

Bing Wan ◽

Li Zhou ◽

Cen Chen ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Alveolar Macrophages ◽

Macrophage Activation ◽

Nuclear Translocation ◽

Inflammatory Responses ◽

Alveolar Epithelium ◽

Geranylgeranyl Diphosphate Synthase ◽

Geranylgeranyl Diphosphate

Macrophage activation is a key contributing factor for excessive inflammatory responses of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Geranylgeranyl diphosphate synthase (GGPPS) plays a key role in the development of inflammatory diseases. Our group previously showed that GGPPS in alveolar epithelium have deleterious effects on acute lung injury induced by LPS or mechanical ventilation. Herein, we examined the role of GGPPS in modulating macrophage activation in ALI/ARDS. We found significant increased GGPPS expression in alveolar macrophages in ARDS patients compared to healthy volunteers and in ALI mice induced by LPS. GGPPS-floxed control (GGPPSfl/fl) and myeloid-selective knockout (GGPPSfl/flLysMcre) mice were then generated. Interestingly, using a LPS-induced ALI mouse model, we showed that myeloid-specific GGPPS knockout significantly increased mortality, aggravated lung injury, and increased the accumulation of inflammatory cells, total protein, and inflammatory cytokines in BALF. In vitro, GGPPS deficiency up-regulated the production of LPS-induced IL-6, IL-1β, and TNF-α in alveolar macrophages, bone marrow-derived macrophages (BMDMs), and THP-1 cells. Mechanistically, GGPPS knockout increased phosphorylation and nuclear translocation of NF-κB p65 induced by LPS. In addition, GGPPS deficiency increased the level of GTP-Rac1, which was responsible for NF-κB activation. In conclusion, decreased expression of GGPPS in macrophages aggravates lung injury and inflammation in ARDS, at least partly by regulating Rac1-dependent NF-κB signaling. GGPPS in macrophages may represent a novel therapeutic target in ARDS.

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Exosomes in postshock mesenteric lymph are key mediators of acute lung injury triggering the macrophage activation via Toll‐like receptor 4

The FASEB Journal ◽

10.1096/fj.201700488r ◽

2017 ◽

Vol 32 (1) ◽

pp. 97-110 ◽

Cited By ~ 37

Author(s):

Mitsuaki Kojima ◽

Joao A. Gimenes‐Junior ◽

Theresa W. Chan ◽

Brian P. Eliceiri ◽

Andrew Baird ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Macrophage Activation ◽

Toll Like Receptor ◽

Toll Like Receptor 4 ◽

Mesenteric Lymph

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Alpha 1-antitrypsin ameliorates ventilator-induced lung injury in rats by inhibiting inflammatory responses and apoptosis

Experimental Biology and Medicine ◽

10.1177/1535370217740852 ◽

2017 ◽

Vol 243 (1) ◽

pp. 87-95 ◽

Cited By ~ 3

Author(s):

He Zhu ◽

Jianshuai He ◽

Jia Liu ◽

Xin Zhang ◽

Fengyun Yang ◽

...

Keyword(s):

Mechanical Ventilation ◽

Lung Injury ◽

Inflammatory Responses ◽

Treatment Options ◽

Weight Ratio ◽

Interleukin 10 ◽

Male Rats ◽

Ventilator Induced Lung Injury ◽

Anti Inflammatory ◽

Alpha 1 Antitrypsin

Mechanical ventilation is extensively used to treat patients with lung injury but may result in ventilator-induced lung injury (VILI). The present study investigated the protective effect of alpha 1-antitrypsin (AAT) on VILI. Adult male rats were subjected to sham, ventilation + saline, or ventilation + AAT treatment and lung injuries were evaluated. Peripheral blood and bronchoalveolar lavage fluid (BALF) were obtained to assess systemic and local inflammatory responses, respectively. Mechanical ventilation resulted in lung injury, as evidenced by histological abnormalities as well as elevations in PaO2/FiO2 ratio, the wet-to-dry weight ratio, and the BALF level of proteins. The intravenous administration of AAT significantly improved these parameters of lung function, suggesting a protective role of AAT in VILI. Mechanistically, ventilator-induced inflammation was effectively reduced by AAT, as evidenced by decreases in BALF neutrophil counts, BALF cytokines, and serum adhesion factors. In contrast, anti-inflammatory interleukin-10 in BALF was increased in response to AAT. AAT treatment also inhibited the expression of nuclear factor-κB, Bax, and cleaved caspase-3 while promoting Bcl-2 expression in ventilator-injured lung tissues. AAT treatment can ameliorate VILI by inhibiting inflammatory mediator production and apoptosis. Impact statement Mechanical ventilation has been commonly used to treat patients with lung injury but may result in ventilator-induced lung injury (VILI). Few effective treatment options are currently available to reduce VILI. Alpha 1-antitrypsin (AAT) is an inhibitor of serine protease with anti-inflammatory and antiapoptotic properties, suggesting a possible role in attenuating lung injury. The present study demonstrates that AAT inhibits the development of VILI by modulating inflammation- and apoptosis-related protein expression. Therefore, AAT may be a novel therapeutic agent for acute respiratory distress syndrome patients undergoing mechanical ventilation.

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