Pulmonary and extrapulmonary acute lung injury: inflammatory and ultrastructural analyses

To test whether pulmonary and extrapulmonary acute lung injury (ALI) of identical mechanical compromise would express diverse morphological patterns and immunological pathways. For this purpose, a model of pulmonary (p) and extrapulmonary (exp) ALI with similar functional changes was developed and pulmonary morphology (light and electron microscopy), cytokines levels, and neutrophilic infiltration in the bronchoalveolar lavage fluid (BALF), elastic and collagen fiber content in the alveolar septa, and neutrophil apoptosis in the lung parenchyma were analyzed. BALB/c mice were divided into four groups. In control groups, saline was intratracheally (it, 0.05 ml) instilled and intraperitoneally (ip, 0.5 ml) injected, respectively. In the ALIp and ALIexp groups, mice received E. coli lipopolysaccharide (10 μg it and 125 μg ip, respectively). The changes in lung resistive and viscoelastic pressures and in static elastance, alveolar collapse, and cell content in lung tissue were similar in the ALIp and ALIexp groups. The ALIp group presented a threefold increase in KC (murine function homolog to IL-8) and IL-10 levels in the BALF in relation to ALIexp, whereas IL-6 level showed a twofold increase in ALIp. Neutrophils in the BALF were more frequent in ALIp than in ALIexp. ALIp showed more extensive injury of alveolar epithelium, intact capillary endothelium, and apoptotic neutrophils, whereas the ALIexp group presented interstitial edema and intact type I and II cells and endothelial layer. In conclusion, given the same pulmonary mechanical dysfunction independently of the etiology of ALI, insult in pulmonary epithelium yielded more pronounced inflammatory responses, which induce ultrastructural morphological changes.

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Effect of MiR-16 on Acute Lung Injury in Neonatal Rats Through Regulating NF-κB Pathway

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2020.2263 ◽

2020 ◽

Vol 10 (3) ◽

pp. 360-364

Author(s):

Yan Xing ◽

Yuan Liang ◽

Changsong Shi ◽

Yudong Miao ◽

Jianqin Gu ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Correlation Analysis ◽

Western Blotting ◽

Inflammatory Responses ◽

Morphological Changes ◽

Pearson Correlation ◽

Mrna Levels ◽

Low Oxygen ◽

Pearson Correlation Analysis

Acute lung injury represents a widespread, variable type of lung injury characterized by a low oxygen level in the blood, non cardiogenic pulmonary edema, low lung compliance and extensive capillary leakage. In our study, the Wistar rat mode of ALI was established using lipopolysaccharide (LPS). The rats were randomly divided into normal control (NC) group (n = 12) and miR-16 overex-pression group (n = 12), and they were transfected with empty vector and miR-16 overexpression virus, respectively. The lung tissues were extracted in both groups, and then the expression levels of miR-16 and NF-κB were detected via fluorescence quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and the association between their expressions was analyzed via Pearson correlation analysis. Moreover, the morphological changes in lung tissues were detected via hematoxylin-eosin (HE) staining, and the differences in the wet/dry weight (W/D) ratio and the pathomorphological score of lung tissues were compared between the two groups. The expression level of NF-κB was detected via immunohistochemistry (IHC) and Western blotting. Our results showed that, there were different degrees of lung injury in lung tissues in both groups. In miR-16 overexpression group, the W/D ratio was significantly higher than that in NC group (P < 0.05), and the pathomorphological score was also significantly higher than that in NC group (P < 0.05). The results of RT-PCR revealed that the mRNA levels of miR-16 and NF-κB in miR-16 overexpression group were 2.5 and 3.7 times higher than those in NC group. The results of Western blotting and IHC also showed that the activity of NF-κB in lung tissues was evidently enhanced in miR-16 overexpression group compared with that in NC group. According to the Pearson correlation analysis, there was a significant positive correlation between the mRNA levels of miR-16 and NF-κB in lung tissues (r = 0.705, P = 0.012). In conclusion, miR-16 activates the NF-κB pathway to initiate a series of inflammatory responses, thereby contributing to the occurrence of ALI in rats.

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The cell biology and pathogenic role of pulmonary intravascular macrophages

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1990.258.2.l1 ◽

1990 ◽

Vol 258 (2) ◽

pp. L1-L12 ◽

Cited By ~ 2

Author(s):

A. E. Warner ◽

J. D. Brain

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Cell Biology ◽

Morphological Characteristics ◽

Laboratory Animals ◽

Capillary Endothelium ◽

Phagocytic Cells ◽

Pulmonary Uptake ◽

Pulmonary Intravascular Macrophages

Pulmonary intravascular macrophages (PIMs) are an extensive population of mature phagocytic cells adherent to the pulmonary capillary endothelium in selected species. They are not prevalent in lungs of commonly studied laboratory animals, such as rodents, and thus have only been recently appreciated. However, their potential role in host defense and acute lung injury has attracted interest, since a number of studies have demonstrated pulmonary localization of circulating particles, microbes, and endotoxin by PIMs. Those animal species, such as ruminants, that provide useful models of pathogen (or endotoxin)-induced acute lung injury demonstrate rapid pulmonary uptake of bacteria by PIMs. Inflammatory mediators released by activated PIMs may initiate the process and provoke accumulation of neutrophils and platelets. This review summarizes the morphological characteristics of PIMs and their species distribution. The role of these members of the mononuclear phagocyte system, both beneficial and potentially pathogenic, is reviewed. The question of whether PIMs have a role in acute lung injury in humans is also discussed.

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Pulmonary Capillary Endothelium-Bound Angiotensin-Converting Enzyme Activity in Acute Lung Injury

Circulation ◽

10.1161/01.cir.102.16.2011 ◽

2000 ◽

Vol 102 (16) ◽

pp. 2011-2018 ◽

Cited By ~ 77

Author(s):

Stylianos E. Orfanos ◽

Apostolos Armaganidis ◽

Constantinos Glynos ◽

Ekaterini Psevdi ◽

Panagiotis Kaltsas ◽

...

Keyword(s):

Enzyme Activity ◽

Acute Lung Injury ◽

Lung Injury ◽

Angiotensin Converting Enzyme ◽

Capillary Endothelium ◽

Converting Enzyme ◽

Angiotensin Converting Enzyme Activity ◽

Pulmonary Capillary

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LncRNA HOTAIR Increases Inflammatory Responses by Activating NF-κB Pathway in LPS-Induced Acute Lung Injury

10.21203/rs.3.rs-49969/v1 ◽

2020 ◽

Author(s):

XiaoMei Huang ◽

ZeXun Mo ◽

YuJun Li ◽

Hua He ◽

KangWei Wang ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Noncoding Rna ◽

Nuclear Translocation ◽

Inflammatory Responses ◽

A549 Cells ◽

Enzyme Linked Immunosorbent Assay ◽

Qrt Pcr ◽

Tnf Α ◽

Lncrna Hotair

Abstract Background Nuclear factor kappa-B (NF-κB) activation increased the expression of cytokines and further lead to lung injury was considered the main mechanism of acute lung injury (ALI). Here, we focus on exploring the potential regulatory mechanism between long noncoding RNA (LncRNA) HOX transcript antisense RNA (HOTAIR) and NF-κB on LPS-induced ALI. Methods A549 cells were then divided into 4 groups: HOTAIR group, NC group, si-HOTAIR group and si-NC group. These 4 groups were then treated with 1μg/mL lipopolysaccharides (LPS) or without LPS at 37°C for 24 h. The expression level of cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6) and LncRNA HOTAIR were evaluated by quantitative Real Time Polymerase Chain Reaction (qRT-PCR) and Enzyme-linked immunosorbent assay (ELISA). Western Blot analysis was adopted for evaluating the level of p-IκBα/IκBα and p-p65/p65. Nuclear translocation of p65 was observed by immunofluorescence staining. Results qRT-PCR and ELISA assay showed that the expression of cytokines (IL-1β, IL-6 and TNF-α) and inflammatory gene HOTAIR was remarkably increased with LPS treatment (p < 0.01). Over-expression of HOTAIR significantly increased the expression of cytokines (including IL-1β, IL-6 and TNF-α) and NF-κB pathway associated proteins (including p-IκBα/IκBα and p-p65/p65), while knockdown of HOTAIR had the opposite effect (p < 0.01). The immunofluorescence assay showed that the level of p65 in the nucleus was significantly higher in the HOTAIR group and significantly lowers in the si-HOTAIR group (p < 0.01). Conclusion HOTAIR may play a pro-inflammatory response through NF-κB pathway in LPS-induced ALI, which may provide a perspective for further understanding the pathogenic mechanism of ALI.

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Levonadifloxacin, a Novel Benzoquinolizine Fluoroquinolone, Modulates Lipopolysaccharide-Induced Inflammatory Responses in Human Whole-Blood Assay and Murine Acute Lung Injury Model

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00084-20 ◽

2020 ◽

Vol 64 (5) ◽

Author(s):

Anasuya Patel ◽

Ganesh V. Sangle ◽

Jinal Trivedi ◽

Sushant A. Shengule ◽

Deepak Thorve ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Whole Blood ◽

Inflammatory Responses ◽

Immunomodulatory Activity ◽

Human Whole Blood ◽

Injury Model ◽

Cytokine Levels ◽

Lung Injury Model ◽

Clinical Benefits

ABSTRACT Fluoroquinolones are reported to possess immunomodulatory activity; hence, a novel benzoquinolizine fluoroquinolone, levonadifloxacin, was evaluated in lipopolysaccharide-stimulated human whole-blood (HWB) and mouse acute lung injury (ALI) models. Levonadifloxacin significantly mitigated the inflammatory responses in an HWB assay through inhibition of proinflammatory cytokines and in the ALI model by lowering lung total white blood cell count, myeloperoxidase, and cytokine levels. The immunomodulatory effect of levonadifloxacin, along with promising antibacterial activity, is expected to provide clinical benefits in the treatment of infections.

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Umbelliferone Alleviates Lipopolysaccharide-Induced Inflammatory Responses in Acute Lung Injury by Down-Regulating TLR4/MyD88/NF-κB Signaling

Inflammation ◽

10.1007/s10753-018-00953-4 ◽

2019 ◽

Vol 42 (2) ◽

pp. 440-448 ◽

Cited By ~ 9

Author(s):

Dongqiu Wang ◽

Xia Wang ◽

Wen Tong ◽

Yuhong Cui ◽

Xiuxian Li ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Inflammatory Responses

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Src protein tyrosine kinase family and acute inflammatory responses

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00261.2005 ◽

2006 ◽

Vol 291 (2) ◽

pp. L129-L141 ◽

Cited By ~ 111

Author(s):

Daisuke Okutani ◽

Monika Lodyga ◽

Bing Han ◽

Mingyao Liu

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Tyrosine Kinase ◽

Reperfusion Injury ◽

Protein Tyrosine Kinase ◽

Inflammatory Responses ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Critical Role ◽

Protein Tyrosine

Acute inflammatory responses are one of the major underlying mechanisms for tissue damage of multiple diseases, such as ischemia-reperfusion injury, sepsis, and acute lung injury. By use of cellular and molecular approaches and transgenic animals, Src protein tyrosine kinase (PTK) family members have been identified to be essential for the recruitment and activation of monocytes, macrophages, neutrophils, and other immune cells. Src PTKs also play a critical role in the regulation of vascular permeability and inflammatory responses in tissue cells. Importantly, animal studies have demonstrated that small chemical inhibitors for Src PTKs attenuate tissue injury and improve survival from a variety of pathological conditions related to acute inflammatory responses. Further investigation may lead to the clinical application of these inhibitors as drugs for ischemia-reperfusion injury (such as stroke and myocardial infarction), sepsis, acute lung injury, and multiple organ dysfunction syndrome.

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