scholarly journals Lung Injury after In Vivo  Reperfusion

2008 ◽  
Vol 109 (2) ◽  
pp. 269-278 ◽  
Author(s):  
Idit Matot ◽  
Sharon Einav ◽  
Carolyn F. Weiniger ◽  
Ron G. Pearl ◽  
Rinat Abramovitch ◽  
...  
Keyword(s):  
Lung Injury ◽  
Lower Lobe ◽  
Receptor Activation ◽  
Left Lower Lobe ◽  
Lung Edema ◽  
Lung Lobe ◽  
Time Period ◽  
Adenosine Receptor Agonist ◽  
A3 Adenosine Receptor

Background Although short-term findings after lung reperfusion have been extensively reported, in vivo animal studies have not described outcome beyond the immediate time period. Therefore, the authors evaluated lung injury 27 h after reperfusion. They also investigated whether attenuation of lung injury with the A3 adenosine receptor agonist MRS3558 was sustained beyond the immediate time period. Methods In intact-chest, spontaneously breathing cats in which the left lower lung lobe was isolated and subjected to 2 h of ischemia and 3 h of reperfusion, MRS3558 was administered before reperfusion. Animals were killed 3 or 27 h after reperfusion. Results When compared with 3 h of reperfusion, at 27 h the left lower lobe showed reduced apoptosis and no change in inflammation, but increased edema. Increased edema of the nonischemic right lung and hypoxemia were observed at 27 h after left lower lobe reperfusion. Increases in phosphorylated p38 levels were found at 3 h of reperfusion compared with control lung, with further increases at 27 h. The attenuation of injury observed with MRS3558 treatment at 3 h of reperfusion was sustained at 27 h. Conclusions Lung edema may worsen hours after the immediate postreperfusion period, even though lung apoptosis and inflammation are reduced or show no change, respectively. This was associated with further increases in phosphorylated p38 levels. The nonischemic lung may also be affected, suggesting a systemic response to reperfusion. In addition, early attenuation of injury is beneficial beyond the immediate period after reperfusion. Treatment aimed at inhibiting p38 activation, such as A3 receptor activation, should be further studied to explore its potential long-term beneficial effect.

Evidence for reprogramming of monocytes into reparative alveolar macrophages in vivo by targeting PDE4b

2021 ◽  
Author(s):  
Ian Rochford ◽  
Jagdish Chandra Joshi ◽  
Rayees Sheikh ◽  
Mumtaz Anwar ◽  
Md Zahid Akhter ◽  
...  
Keyword(s):  
Lung Injury ◽  
Alveolar Macrophages ◽  
Lung Edema ◽  
Rna Seq ◽  
Activation Of Transcription ◽  
The Impact ◽  
Camp Levels ◽  
Phosphodiesterase 4B ◽  
Lung Vascular Permeability

Increased lung vascular permeability and neutrophilic inflammation are hallmarks of acute lung injury. Alveolar macrophages (AMϕ), the predominant sentinel cell type in the airspace, die in massive numbers while fending off pathogens. Recent studies indicate that the AMϕ pool is replenished by airspace-recruited monocytes, but the mechanisms instructing the conversion of recruited monocytes into reparative AMϕ remain elusive. Cyclic AMP (cAMP) is a vascular barrier protective and immunosuppressive second messenger in the lung. Here, we subjected mice expressing GFP under the control of the Lysozyme-M promoter (LysM-GFP mice) to the LPS model of rapidly resolving lung injury to address the impact of mechanisms determining cAMP levels in AMϕ and regulation of mobilization of the reparative AMϕ-pool. RNA-seq analysis of flow-sorted Mϕ identified phosphodiesterase 4b (PDE4b) as the top LPS-responsive cAMP-regulating gene. We observed that PDE4b expression markedly increased at the time of peak injury (4 h) and then decreased to below the basal level during the resolution phase (24 h). Activation of transcription factor NFATc2 was required for transcription of PDE4b in Mϕ. Inhibition of PDE4 activity at the time of peak injury, using i.t. rolipram, increased cAMP levels, augmented the reparative AMϕ pool, and resolved lung injury. This response was not seen following conditional depletion of monocytes, thus establishing airspace-recruited PDE4b-sensitive monocytes as the source of reparative AMϕ. Interestingly, adoptive transfer of rolipram-educated AMϕ into injured mice resolved lung edema. We propose suppression of PDE4b as an effective approach to promote reparative AMϕ generation from monocytes for lung repair.

Surfactant treatments alter endogenous surfactant metabolism in rabbit lungs

1990 ◽  
Vol 68 (4) ◽  
pp. 1590-1596 ◽  
Author(s):  
S. B. Oetomo ◽  
J. Lewis ◽  
M. Ikegami ◽  
A. H. Jobe
Keyword(s):  
Lower Lobe ◽  
Left Lower Lobe ◽  
Exogenous Surfactant ◽  
Main Stem Bronchus ◽  
Label Incorporation ◽  
Left Main Stem Bronchus ◽  
The Right ◽  
Surfactant Metabolism

The effect of exogenous surfactant on endogenous surfactant metabolism was evaluated using a single-lobe treatment strategy to compare effects of treated with untreated lung within the same rabbit. Natural rabbit surfactant, Survanta, or 0.45% NaCl was injected into the left main stem bronchus by use of a Swan-Ganz catheter. Radio-labeled palmitic acid was then given by intravascular injection at two times after surfactant treatment, and the ratios of label incorporation and secretion in the left lower lobe to label incorporation and secretion in the right lung were compared. The treatment procedure resulted in a reasonably uniform surfactant distribution and did not disrupt lobar pulmonary blood flow. Natural rabbit surfactant increased incorporation of palmitate into saturated phosphatidylcholine (Sat PC) approximately 2-fold (P less than 0.01), and secretion of labeled Sat PC increased approximately 2.5-fold in the surfactant-treated left lower lobe relative to the right lung (P less than 0.01). Although Survanta did not alter incorporation, it did increase secretion but not to the same extent as rabbit surfactant (P less than 0.01). Alteration of endogenous surfactant Sat PC metabolism in vivo by surfactant treatments was different from that which would have been predicted by previous in vitro studies.

Forces involved in lobar atelectasis in intact dogs

1980 ◽  
Vol 48 (1) ◽  
pp. 29-33 ◽  
Author(s):  
G. T. Ford ◽  
C. A. Bradley ◽  
N. R. Anthonisen
Keyword(s):  
Chest Wall ◽  
Lower Lobe ◽  
Transpulmonary Pressure ◽  
Esophageal Pressure ◽  
Lateral Position ◽  
Relative Volume ◽  
Left Lower Lobe ◽  
Lung Lobe ◽  
Left Lateral Position ◽  
The Difference

When an excised lung lobe undergoes atelectasis, its shape differs from that observed when lobar atelectasis occurs in an intact animal: the chest wall deforms the collapsing lobe. In eight anesthetized dogs in the left lateral position we measured lung volume and transpulmonary pressure during the development of atelectasis. We then induced atelectasis of the left lower lobe with the rest of the lung maintained at FRC and measured lobar volume and "translobar" (lobar minus esophageal) pressure. Lung and lobar volumes were measured by prebreathing the animal with 88% O2-12% N2, occluding the airway and observing the increase in lung or lobar N2 concentration. When the left lower lobe alone collapsed, translobar pressures were more negative than transpulmonary pressure at the same relative volume when the whole lung collapsed. This pressure difference, which represents the deforming force applied to the lobe minus the pressure costs of deformation, averaged 3 cmH2O at 50% FRC. Infusion of 25 ml of normal saline into the pleural space sharply reduced the difference pulmonary pressure during lung collapse: this difference was abolished at 80% FRC and halved at 50% FRC. The large effect of the small volume of fluid suggested that deforming forces were largely generated in relatively local areas, such as regions of the chest wall with sharp angulation.

scholarly journals PKR-dependent CHOP induction limits hyperoxia-induced lung injury

2011 ◽  
Vol 300 (3) ◽  
pp. L422-L429 ◽  
Author(s):  
Tricia I. Lozon ◽  
Alison J. Eastman ◽  
Gustavo Matute-Bello ◽  
Peter Chen ◽  
Teal S. Hallstrand ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lung Injury ◽  
Er Stress ◽  
Initiation Factor ◽  
Mouse Lung ◽  
Epithelial Cell Line ◽  
Lung Edema ◽  
Α Subunit ◽  
Chop Expression

Supplemental O2is commonly employed in patients with respiratory failure; however, hyperoxia is also a potential contributor to lung injury. In animal models, hyperoxia causes oxidative stress in the lungs, resulting in increased inflammation, edema, and permeability. We hypothesized that oxidative stress from prolonged hyperoxia leads to endoplasmic reticulum (ER) stress, resulting in activation of the unfolded protein response (UPR) and induction of CCAAT enhancer-binding protein homologous protein (CHOP), a transcription factor associated with cell death in the setting of persistent ER stress. To test this hypothesis, we exposed the mouse lung epithelial cell line MLE-12 to 95% O2for 8–24 h and evaluated for evidence of UPR induction and CHOP induction. Hyperoxia caused increased CHOP expression without other evidence of UPR activation. Because CHOP expression is preceded by phosphorylation of the α-subunit of the eukaryotic initiation factor-2 (eIF2α), we evaluated the role of double-stranded RNA-activated protein kinase (PKR), a non-UPR-associated eIF2α kinase. Hyperoxia caused PKR phosphorylation, and RNA interference knockdown of PKR attenuated hyperoxia-induced CHOP expression. In vivo, hyperoxia induced PKR phosphorylation and CHOP expression in the lungs without other biochemical evidence for ER stress. Additionally, Ddit3−/−(CHOP-null) mice had increased lung edema and permeability, indicating a previously unknown protective role for CHOP after prolonged hyperoxia. We conclude that hyperoxia increases CHOP expression via an ER stress-independent, PKR-dependent pathway and that increased CHOP expression protects against hyperoxia-induced lung injury.

scholarly journals Tanreqing Inhibits LPS-Induced Acute Lung Injury In Vivo and In Vitro Through Downregulating STING Signaling Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Yu-Qiong He ◽  
Can-Can Zhou ◽  
Jiu-Ling Deng ◽  
Liang Wang ◽  
Wan-Sheng Chen
Keyword(s):  
Oxidative Stress ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Signaling Pathway ◽  
Inflammatory Responses ◽  
Lung Edema ◽  
Protective Effects ◽  
And Oxidative Stress

Acute lung injury (ALI) is a common life-threatening lung disease, which is mostly associated with severe inflammatory responses and oxidative stress. Tanreqing injection (TRQ), a Chinese patent medicine, is clinically used for respiratory-related diseases. However, the effects and action mechanism of TRQ on ALI are still unclear. Recently, STING as a cytoplasmic DNA sensor has been found to be related to the progress of ALI. Here, we showed that TRQ significantly inhibited LPS-induced lung histological change, lung edema, and inflammatory cell infiltration. Moreover, TRQ markedly reduced inflammatory mediators release (TNF-α, IL-6, IL-1β, and IFN-β). Furthermore, TRQ also alleviated oxidative stress, manifested by increased SOD and GSH activities and decreased 4-HNE, MDA, LDH, and ROS activities. In addition, we further found that TRQ significantly prevented cGAS, STING, P-TBK, P-P65, P-IRF3, and P-IκBα expression in ALI mice. And we also confirmed that TRQ could inhibit mtDNA release and suppress signaling pathway mediated by STING in vitro. Importantly, the addition of STING agonist DMXAA dramatically abolished the protective effects of TRQ. Taken together, this study indicated that TRQ alleviated LPS-induced ALI and inhibited inflammatory responses and oxidative stress through STING signaling pathway.

scholarly journals CB2 Receptor Activation Ameliorates the Proinflammatory Activity in Acute Lung Injury Induced by Paraquat

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Zhenning Liu ◽  
Yu Wang ◽  
Hongyu Zhao ◽  
Qiang Zheng ◽  
Li Xiao ◽  
...  
Keyword(s):  
Lung Injury ◽  
Cannabinoid Receptor ◽  
Dry Weight ◽  
Lavage Fluid ◽  
Receptor Activation ◽  
Lung Edema ◽  
Myeloperoxidase Activity ◽  
Cb2 Receptor ◽  
Arterial Blood ◽  
Proinflammatory Activity

Paraquat, a widely used herbicide, is well known to exhibit oxidative stress and lung injury. In the present study, we investigated the possible underlying mechanisms of cannabinoid receptor-2 (CB2) activation to ameliorate the proinflammatory activity induced by PQ in rats. JWH133, a CB2 agonist, was administered by intraperitoneal injection 1 h prior to PQ exposure. After PQ exposure for 4, 8, 24, and 72 h, the bronchoalveolar lavage fluid was collected to determine levels of TNF-αand IL-1β, and the arterial blood samples were collected for detection of PaO2level. At 72 h after PQ exposure, lung tissues were collected to determine the lung wet-to-dry weight ratios, myeloperoxidase activity, lung histopathology, the protein expression level of CB2, MAPKs (ERK1/2, p38MAPK, and JNK1/2), and NF-κBp65. After rats were pretreated with JWH133, PQ-induced lung edema and lung histopathological changes were significantly attenuated. PQ-induced TNF-αand IL-1βsecretion in BALF, increases of PaO2in arterial blood, and MPO levels in the lung tissue were significantly reduced. JWH133 could efficiently activate CB2, while inhibiting MAPKs and NF-κB activation. The results suggested that activating CB2 receptor exerted protective activity against PQ-induced ALI, and it potentially contributed to the suppression of the activation of MAPKs and NF-κB pathways.

scholarly journals Design and in vivo activity of A3 adenosine receptor agonist prodrugs

2020 ◽  
Vol 16 (3) ◽  
pp. 367-377 ◽  
Author(s):  
R. Rama Suresh ◽  
Shanu Jain ◽  
Zhoumou Chen ◽  
Dilip K. Tosh ◽  
Yanling Ma ◽  
...  
Keyword(s):  
Adenosine Receptor ◽  
Receptor Agonist ◽  
Adenosine Receptor Agonist ◽  
A3 Adenosine Receptor

Effect of intravenous catalase on the pulmonary vascular response to endotoxemia in goats

1988 ◽  
Vol 64 (2) ◽  
pp. 697-704 ◽  
Author(s):  
R. J. Maunder ◽  
R. K. Winn ◽  
J. M. Gleisner ◽  
J. Hildebrandt ◽  
J. M. Harlan
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Endothelial Damage ◽  
In Vivo Model ◽  
Lung Edema ◽  
Experimental Sepsis ◽  
Base Line ◽  
In Vitro Systems

Neutrophils have been implicated in the pathogenesis of acute lung injury associated with clinical and experimental sepsis. Data from in vitro systems and experimental animals have suggested that neutrophil-derived oxidants, particularly H2O2, may be primarily responsible for endothelial damage, vasoconstriction, and lung edema. With the use of endotoxin infusion as an in vivo model of sepsis we tested the hypothesis that pretreatment with catalase, a peroxide scavenger, would ameliorate the resultant changes in pulmonary vasoconstriction and lung fluid balance. Paired experiments were performed in 16 goats with chronic lung lymph fistulas. One group of animals (n = 7) received endotoxin first alone and then again, several days later, after pretreatment with Ficoll-linked catalase. As a control, identical experiments were performed in a separate group (n = 6) with Ficoll-linked albumin substituted for Ficoll-catalase. A third group (n = 3) was given endotoxin alone and then again during a continuous infusion of catalase. Plasma and lymph levels of catalase were comparable to or exceeded those previously shown to be completely protective in isolated perfused lung preparations and in vitro systems. Endotoxin caused neutropenia, pulmonary arterial hypertension, decreased cardiac output, and increases in lymph flow to approximately three times base line, with a return of all variables toward control values by 6 h. Catalase pretreatment produced no significant differences in any of these variables. These experiments do not support a role for H2O2 as a mediator of acute lung injury due to endotoxemia.

scholarly journals Myricetin Attenuates LPS-induced Inflammation in RAW 264.7 Macrophages and Mouse Models

2018 ◽  
Author(s):  
Wei Hou ◽  
Siyi Hu ◽  
Zhenzhong Su ◽  
Qi Wang ◽  
Guangping Meng ◽  
...  
Keyword(s):  
Lung Injury ◽  
Macrophage Activation ◽  
Weight Ratio ◽  
Mapk Signaling ◽  
Raw264.7 Cells ◽  
Lung Edema ◽  
Raw 264.7 ◽  
The Impact

AbstractBackgroundMyricetin has been demonstrated to inhibit inflammation in a variety of diseases, but little is known about its characters in acute lung injury (ALI). In this study, we aimed to investigate the protective effects of myricetin on inflammation in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and a LPS-induced lung injury model.MethodsSpecifically, we investigated its effects on lung edema and histological damage by lung W/D weight ratio, HE staining and Evans Blue dye. Then macrophage activation was detected by evaluating the TNF-α, IL-6 and IL-1β mRNA and protein iNOS and COX-2. Myricetin was used to detect the impact on the inflammatory responses in LPS-induced RAW264.7 cells with the same manners in mouse model. Finally, NF-κB and MAPK signaling pathways were investigated with Western blot assay in LPS-induced RAW264.7 cells.ResultsMyricetin significantly inhibited the production of the pro-inflammatory cytokines in vitro and in vivo. The in vivo experiments showed that pretreatment with Myricetin markedly attenuated the development of pulmonary edema, histological severities and macrophage activation in mice with ALI. The underlying mechanisms were further demonstrated in vitro that myricetin exerted an anti-inflammatory effect through suppressing the NF-κB p65 and AKT activation in NF-κB pathway and JNK, p-ERK and p38 in mitogen-activated protein kinases signaling pathway.ConclusionMyricetin alleviated ALI by inhibiting macrophage activation, and inhibited inflammation in vitro and in vivo. It may be a potential therapeutic candidate for the prevention of inflammatory diseases.

scholarly journals IN VITRO EVALUATION OF ANTI-CANCER POTENTIAL OF A3 ADENOSINE RECEPTOR AGONIST ON A549 HUMAN LUNG CANCER CELL LINE

2019 ◽  
pp. 106-108
Author(s):  
Nilay D Solanki ◽  
Alkesh Patel ◽  
Leena Patel
Keyword(s):  
Lung Cancer ◽  
Cell Line ◽  
Cancer Cell Line ◽  
Lung Cancer Cell Line ◽  
Human Lung Cancer ◽  
Adenosine Receptor Agonist ◽  
A3 Adenosine Receptor ◽  
Dose Dependent

Objective: The objective of this study was to evaluate the cytotoxic potential of A3AR agonist (ABMECA) against human lung cancer cell line A549 by using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. Methods: Adenocarcinoma cell line A549 was used to assess MTT based cells viability. In vitro cytotoxic activity was evaluated for 3 different concentration of doxorubicin and A3AR by MTT cytotoxicity assay. Cytotoxicity assay carried out for 3 consecutive days that involves culturing cells into Dulbecco’s MEM medium modified with 10% FBS for 24 h then treatment with different dose of standard and test drug with incubation period of 24 h followed by treatment with MTT for estimation of cytotoxicity and finally, optical density (OD) was measured at 570-630 nm. Results: Different concentration of doxorubicin (1, 5, 10 µM) and ABMECA (10-6M, 10-5M and 10-4M) shown dose-dependent cytotoxicity. There was a significant decrease (p<0.05) in cell viability in both doxorubicin and ABMECA concentration in a dose-dependent manner. This study may guide further for in vivo evaluation of test drug in the lung cancer model. Conclusion: A3 Adenosine Receptor agonist could be potential moiety for the treatment of lung cancer and it would require in vivo study for further research.

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