High-volume ventilation induces pentraxin 3 expression in multiple acute lung injury models in rats

2007 ◽  
Vol 292 (1) ◽  
pp. L144-L153 ◽  
Author(s):  
Daisuke Okutani ◽  
Bing Han ◽  
Marco Mura ◽  
Thomas K. Waddell ◽  
Shaf Keshavjee ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
High Volume ◽  
Pentraxin 3 ◽  
Sprague Dawley ◽  
Ventilator Induced Lung Injury ◽  
Sprague Dawley Rats ◽  
Volume Ventilation ◽  
Highly Correlated ◽  
Injury Models

Pentraxin 3 (PTX3) is an acute-phase protein, which can be produced by a variety of tissue cells at the site of infection or inflammation. It plays an important role in innate immunity in the lung and in mediating acute lung injury. The aim of this study was to determine the effect of mechanical ventilation on PTX3 expression in multiple lung injury models. Male Sprague-Dawley rats were challenged with intravenous injection of lipopolysaccharide (LPS) or hemorrhage followed by resuscitation (HS). The animals were then subjected to either relatively higher (12 ml/kg) or lower (6 ml/kg, positive end-expiratory pressure of 5 cmH2O) volume ventilation for 4 h. High-volume ventilation significantly enhanced PTX3 expression in the lung, either alone or in combination with LPS or hemorrhage. A significant increase of PTX3 immunohistochemistry staining in the lung was seen in all injury groups. The PTX3 expression was highly correlated with the severity of lung injury determined by blood gas, lung elastance, and wet-to-dry ratio. To determine the effects of HS, LPS, or injurious ventilation (25 ml/kg) alone on PTX3 expression, another group of rats was studied. Injurious ventilation significantly damaged the lung and increased PTX3 expression. A local expression of PTX3 induced by high-volume ventilation, either alone or in combination with other pathological conditions, suggests that it may be an important mediator in ventilator-induced lung injury.

scholarly journals Activation of cholinergic anti-inflammatory pathway involved in therapeutic actions of α-mangostin on lipopolysaccharide-induced acute lung injury in rats

2020 ◽  
Vol 34 ◽  
pp. 205873842095494
Author(s):  
Zhe Yang ◽  
Qin Yin ◽  
Opeyemi Joshua Olatunji ◽  
Yan Li ◽  
Shu Pan ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Raw 264.7 Cells ◽  
Raw 264.7 ◽  
Sprague Dawley ◽  
Α7 Nicotinic Acetylcholine Receptor ◽  
Inflammatory Pathway ◽  
Inflammatory Reactions ◽  
Sprague Dawley Rats ◽  
Anti Inflammatory

Introduction: Alpha-mangostin (MAN) possesses a wide variety of pharmacological effects. In this study, we investigated its effect on cholinergic anti-inflammatory pathway (CAP), and tested if CAP regulation was involved in the therapeutic action on acute lung injury (ALI). Methods: Male Sprague Dawley rats were pre-treated with MAN (40 mg/kg) for 3 days and ALI was induced with an intraperitoneal injection of lipopolysaccharide (LPS). Certain rats received monolateral vagotomy or sham surgery. The effects on inflammatory reactions and relevant pathways in ALI rats or LPS pre-treated RAW 264.7 cells were investigated by histological, immunohistochemical, immunoblotting, RT-qPCR, and immunofluorescence assays, while levels of proinflammatory cytokines, acetylcholine (Ach) and the enzymatic activity of acetylcholinesterase (AchE) were determined by corresponding quantitative kits. Results: Oral administration of MAN reduced the severity of ALI, while vagotomy surgery antagonized this effect. MAN restored the decline in α7 nicotinic acetylcholine receptor (α7nAchR) in the lungs of ALI rats, and promoted the expression of α7nAchR and choline acetyltransferase (CHAT) in RAW 264.7 cells. Although AchE expression was barely affected by MAN at 5 μg/ml, its catalytic activity was reduced by almost 95%. Extracellular rather than intracellular Ach was notably raised shortly after MAN treatment. Furthermore, MAN at 5 μg/ml effectively inhibited LPS-induced increase in phosphorylation and nucleus translocation of p65 subunit, and secretion of TNF-α and IL-1β, which was then offset by methyllycaconitine citrate hydrate. Conclusion: MAN activated CAP by increasing peripheral Ach and up-regulating α7nAchR expression, which eventually led to NF-κB inhibition and remission of acute inflammations.

scholarly journals Comparison of direct and indirect models of early induced acute lung injury

2020 ◽  
Vol 8 (S1) ◽  
Author(s):  
Laura Chimenti ◽  
Luis Morales-Quinteros ◽  
Ferranda Puig ◽  
Marta Camprubi-Rimblas ◽  
Raquel Guillamat-Prats ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Acute Phase ◽  
Cecal Ligation ◽  
Sprague Dawley ◽  
Acid Aspiration ◽  
Sprague Dawley Rats ◽  
Tnf Α ◽  
Gastric Contents ◽  
Bacterial Superinfection

Abstract Background The animal experimental counterpart of human acute respiratory distress syndrome (ARDS) is acute lung injury (ALI). Most models of ALI involve reproducing the clinical risk factors associated with human ARDS, such as sepsis or acid aspiration; however, none of these models fully replicates human ARDS. Aim To compare different experimental animal models of ALI, based on direct or indirect mechanisms of lung injury, to characterize a model which more closely could reproduce the acute phase of human ARDS. Materials and methods Adult male Sprague-Dawley rats were subjected to intratracheal instillations of (1) HCl to mimic aspiration of gastric contents; (2) lipopolysaccharide (LPS) to mimic bacterial infection; (3) HCl followed by LPS to mimic aspiration of gastric contents with bacterial superinfection; or (4) cecal ligation and puncture (CLP) to induce peritonitis and mimic sepsis. Rats were sacrificed 24 h after instillations or 24 h after CLP. Results At 24 h, rats instilled with LPS or HCl-LPS had increased lung permeability, alveolar neutrophilic recruitment and inflammatory markers (GRO/KC, TNF-α, MCP-1, IL-1β, IL-6). Rats receiving only HCl or subjected to CLP had no evidence of lung injury. Conclusions Rat models of ALI induced directly by LPS or HCl-LPS more closely reproduced the acute phase of human ARDS than the CLP model of indirectly induced ALI.

Clara cell secretory protein and phospholipase A2 activity modulate acute ventilator-induced lung injury in mice

2005 ◽  
Vol 98 (4) ◽  
pp. 1264-1271 ◽  
Author(s):  
Sawako Yoshikawa ◽  
Takashige Miyahara ◽  
Susan D. Reynolds ◽  
Barry R. Stripp ◽  
Mircea Anghelescu ◽  
...  
Keyword(s):  
Lung Injury ◽  
Bronchoalveolar Lavage ◽  
Dry Weight ◽  
High Volume ◽  
Secretory Protein ◽  
Clara Cell ◽  
Wild Type ◽  
Clara Cell Secretory Protein ◽  
Ventilator Induced Lung Injury ◽  
Volume Ventilation

Lung vascular permeability is acutely increased by high-pressure and high-volume ventilation. To determine the roles of mechanically activated cytosolic PLA2 (cPLA2) and Clara cell secretory protein (CCSP), a modulator of cPLA2 activity, we compared lung injury with and without a PLA2 inhibitor in wild-type mice and CCSP-null mice (CCSP−/−) ventilated with high and low peak inflation pressures (PIP) for 2- or 4-h periods. After ventilation with high PIP, we observed significant increases in the bronchoalveolar lavage albumin concentrations, lung wet-to-dry weight ratios, and lung myeloperoxidase in both genotypes compared with unventilated controls and low-PIP ventilated mice. All injury variables except myeloperoxidase were significantly greater in the CCSP−/− mice relative to wild-type mice. Inhibition of cPLA2 in wild-type and CCSP−/− mice ventilated at high PIP for 4 h significantly reduced bronchoalveolar lavage albumin and total protein and lung wet-to-dry weight ratios compared with vehicle-treated mice of the same genotype. Membrane phospho-cPLA2 and cPLA2 activities were significantly elevated in lung homogenates of high-PIP ventilated mice of both genotypes but were significantly higher in the CCSP−/− mice relative to the wild-type mice. Inhibition of cPLA2 significantly attenuated both the phospho-cPLA2 increase and increased cPLA2 activity due to high-PIP ventilation. We propose that mechanical activation of the cPLA2 pathway contributes to acute high PIP-induced lung injury and that CCSP may reduce this injury through inhibition of the cPLA2 pathway and reduction of proinflammatory products produced by this pathway.

scholarly journals Anti-Inflammatory and Anticoagulative Effects of Paeonol on LPS-Induced Acute Lung Injury in Rats

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Pin-Kuei Fu ◽  
Chieh-Liang Wu ◽  
Tung-Hu Tsai ◽  
Ching-Liang Hsieh
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Interleukin 1 ◽  
Intraperitoneal Administration ◽  
Lavage Fluid ◽  
Polymorphonuclear Neutrophils ◽  
Sprague Dawley ◽  
Intratracheal Administration ◽  
Sprague Dawley Rats ◽  
Anti Inflammatory

Paeonol is an active component of Moutan Cortex Radicis and is widely used as an analgesic, antipyretic, and anti-inflammatory agent in traditional Chinese medicine. We wanted to determine the role of paeonol in treating adult respiratory distress syndrome (ARDS). We established an acute lung injury (ALI) model in Sprague-Dawley rats, which was similar to ARDS in humans, using intratracheal administration of lipopolysaccharide (LPS). The intraperitoneal administration of paeonol successfully reduced histopathological scores and attenuated myeloperoxidase-reactive cells as an index of polymorphonuclear neutrophils infiltration and also reduces inducible nitric oxide synthase expression in the lung tissue, at 16 h after LPS administration. In addition, paeonol reduced proinflammatory cytokines in bronchoalveolar lavage fluid, including tumor-necrosis factor-α, interleukin-1β, interleukin-6, and plasminogen-activated inhibition factor-1. These results indicated that paeonol successfully attenuates inflammatory and coagulation reactions to protect against ALI.

Long pentraxin 3 in pulmonary infection and acute lung injury

2007 ◽  
Vol 292 (5) ◽  
pp. L1039-L1049 ◽  
Author(s):  
Xiaolin He ◽  
Bing Han ◽  
Mingyao Liu
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Pulmonary Infection ◽  
Ischemia Reperfusion ◽  
High Volume ◽  
Pentraxin 3 ◽  
Experimental Conditions ◽  
Novel Therapeutic Strategies ◽  
Intestinal Ischemia Reperfusion ◽  
Severe Lung

Long pentraxin 3 (PTX3) is a newly discovered acute phase protein produced at the sites of infection and inflammation by tissue cells, macrophages, monocytes, and dendritic cells. PTX3 plays an important role in preventing infection of certain fungi, bacteria, and viruses in the lung. Recombinant PTX3 has been proposed as a potential antifungal molecule for therapy. However, under certain experimental conditions, such as intestinal ischemia-reperfusion, high volume mechanical ventilation, or severe bacterial infection, increased expression of PTX3 is associated with more severe lung injury. Therefore, it is necessary to further explore the sources of PTX3 in the lung and the regulatory mechanisms of its expression. It is also essential to further determine how PTX3 binds to pathogens, complement, and apoptotic cells, and to determine whether PTX3 has a specific receptor in targeted cells. These studies will provide insight into the pathological processes of pulmonary infection and acute lung injury and provide potential novel therapeutic strategies to control pulmonary infections without severe lung injury.

scholarly journals Knockdown of lung phosphodiesterase 2A attenuates alveolar inflammation and protein leak in a two-hit mouse model of acute lung injury

2011 ◽  
Vol 301 (2) ◽  
pp. L161-L170 ◽  
Author(s):  
Otgonchimeg Rentsendorj ◽  
Mahendra Damarla ◽  
Neil R. Aggarwal ◽  
Ji-Young Choi ◽  
Laura Johnston ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Mouse Model ◽  
Time Course ◽  
Fold Increase ◽  
Ventilator Induced Lung Injury ◽  
Volume Ventilation ◽  
Mrna And Protein Expression ◽  
Oxide Synthase ◽  
Synergistic Increase

Phosphodiesterase 2A (PDE2A) is stimulated by cGMP to hydrolyze cAMP, a potent endothelial barrier-protective molecule. We previously found that lung PDE2A contributed to a mouse model of ventilator-induced lung injury (VILI). The purpose of the present study was to determine the contribution of PDE2A in a two-hit mouse model of 1-day intratracheal (IT) LPS followed by 4 h of 20 ml/kg tidal volume ventilation. Compared with IT water controls, LPS alone (3.75 μg/g body wt) increased lung PDE2A mRNA and protein expression by 6 h with a persistent increase in protein through day 4 before decreasing to control levels on days 6 and 10. Similar to the PDE2A time course, the peak in bronchoalveolar lavage (BAL) neutrophils, lactate dehydrogenase (LDH), and protein concentration also occurred on day 4 post-LPS. IT LPS (1 day) and VILI caused a threefold increase in lung PDE2A and inducible nitric oxide synthase (iNOS) and a 24-fold increase in BAL neutrophilia. Compared with a control adenovirus, PDE2A knockdown with an adenovirus expressing a short hairpin RNA administered IT 3 days before LPS/VILI effectively decreased lung PDE2A expression and significantly attenuated BAL neutrophilia, LDH, protein, and chemokine levels. PDE2A knockdown also reduced lung iNOS expression by 53%, increased lung cAMP by nearly twofold, and improved survival from 47 to 100%. We conclude that in a mouse model of LPS/VILI, a synergistic increase in lung PDE2A expression increased lung iNOS and alveolar inflammation and contributed significantly to the ensuing acute lung injury.

scholarly journals Effect of rapamycin on early stage apoptosis of neutrophils in Sprague-Dawley rats with acute lung injury

2017 ◽  
Vol 7 (2) ◽  
pp. 148-152
Author(s):  
Liwei Li ◽  
Changtai Zhu ◽  
Ye Yuan ◽  
Zhiqiang Li
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Early Stage ◽  
Sprague Dawley ◽  
Sprague Dawley Rats

scholarly journals Remote Inflammatory Preconditioning Alleviates Lipopolysaccharide-Induced Acute Lung Injury via Inhibition of Intrinsic Apoptosis in Rats

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Yong Liu ◽  
Jiahang Xu ◽  
Liang Zhao ◽  
Jing Cheng ◽  
Baojun Chen
Keyword(s):  
Oxidative Stress ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Animal Experiments ◽  
Intrinsic Apoptosis ◽  
Sprague Dawley ◽  
Sod Activity ◽  
Lung Protection ◽  
Sprague Dawley Rats ◽  
The Right

Background. Acute lung injury (ALI) always leads to severe inflammation. As inflammation and oxidative stress are the common pathological basis of endotoxin-induced inflammatory injury and ischemic reperfusion injury (IRI), we speculate that remote ischemic preconditioning (RIPC) can be protective for ALI when used as remote inflammatory preconditioning (RInPC). Method. A total of 21 Sprague-Dawley rats were used for the animal experiments. Eighteen rats were equally and randomly divided into the control (NS injection), LPS (LPS injection), and RInPC groups. The RInPC was performed prior to the LPS injection via tourniquet blockage of blood flow to the right hind limb and adopted three cycles of 5 min tying followed by 5 min untying. Animals were sacrificed 24 hours later. There were 2 rats in the LPS group and 1 in the RInPC group who died before the end of the experiment. Supplementary experiments in the LPS and RInPC groups were conducted to ensure that 6 animals in each group reached the end of the experiment. Results. In the present study, we demonstrated that the RInPC significantly attenuated the LPS-induced ALI in rats. Apoptotic cells were reduced significantly by the RInPC, with the simultaneous improvement of apoptosis-related proteins. Reduction of MPO and MDA and increasing of SOD activity were found significantly improved by the RInPC. Increasing of TNF-α, IL-1β, and IL-6 induced by the LPS was inhibited, while IL-10 was significantly increased by RInPC, compared to the LPS group. Conclusion. RInPC could inhibit inflammation and attenuate oxidative stress, thereby reducing intrinsic apoptosis and providing lung protection in the LPS-induced ALI in rats.

Ischemia-reperfusion lung injury attenuated by ATP-MgCl2 in rats

1994 ◽  
Vol 76 (2) ◽  
pp. 545-552 ◽  
Author(s):  
K. Hsu ◽  
D. Wang ◽  
S. Y. Wu ◽  
C. Y. Shen ◽  
H. I. Chen
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Protective Effect ◽  
Degradation Product ◽  
Ischemia Reperfusion ◽  
Protective Effects ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Kidney Liver ◽  
A2 Receptors

The protective effect of ATP-MgCl2 on ischemia-reperfusion lung injury has been reported in kidney, liver, heart, and muscle but has not been examined in lungs. The aim of this study was to determine whether ATP or ATP-MgCl2 pretreatment would attenuate ischemia-reperfusion-induced acute lung injury and to identify the possible mechanisms for such protection. Typical acute lung injury was successfully induced in Sprague-Dawley rats by 10 min of hypoxia followed by 75 min of ischemia and 50 min of reperfusion. Pretreatment with ATP-MgCl2 (or adenosine) but not ATP or MgCl2 (all at 10(-6) M) significantly attenuated the acute lung injury. All the protective effects of ATP-MgCl2 were nearly undetectable when promazine (an ecto-adenosinetriphosphatase inhibitor) or 3,7-dimethyl-1-propargylxanthine (an A2-receptor antagonist) was added before ATP-MgCl2 pretreatment. These observations support our hypothesis that the protective effect of ATP-MgCl2 is in part mediated through adenosine, the degradation product of ATP, which is produced by the Mg(2+)-dependent ecto-adenosinetriphosphatase on the surface of neutrophils and reacts with neutrophil A2 receptors to inhibit the production of O2 radicals.

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