scholarly journals Pulmonary Surfactant and Bacterial Lipopolysaccharide: The Interaction and its Functional Consequences

2017 ◽  
pp. S147-S157 ◽  
Author(s):  
M. KOLOMAZNIK ◽  
Z. NOVA ◽  
A. CALKOVSKA
Keyword(s):  
Lung Injury ◽  
Respiratory System ◽  
Pulmonary Surfactant ◽  
Intratracheal Instillation ◽  
Clinical Importance ◽  
Inflammatory Cells ◽  
Blood Stream ◽  
Surfactant Molecule ◽  
Exogenous Surfactant ◽  
Alveolar Type

The respiratory system is constantly exposed to pathogens which enter the lungs by inhalation or via blood stream. Lipopolysaccharide (LPS), also named endotoxin, can reach the airspaces as the major component of the outer membrane of Gram-negative bacteria, and lead to local inflammation and systemic toxicity. LPS affects alveolar type II (ATII) cells and pulmonary surfactant and although surfactant molecule has the effective protective mechanisms, excessive amount of LPS interacts with surfactant film and leads to its inactivation. From immunological point of view, surfactant specific proteins (SPs) SP-A and SP-D are best characterized, however, there is increasing evidence on the involvement of SP-B and SP-C and certain phospholipids in immune reactions. In animal models, the instillation of LPS to the respiratory system induces acute lung injury (ALI). It is of clinical importance that endotoxin-induced lung injury can be favorably influenced by intratracheal instillation of exogenous surfactant. The beneficial effect of this treatment was confirmed for both natural porcine and synthetic surfactants. It is believed that the surfactant preparations have anti-inflammatory properties through regulating cytokine production by inflammatory cells. The mechanism by which LPS interferes with ATII cells and surfactant layer, and its consequences are discussed below.

scholarly journals Anti-Inflammatory Effects of Monoammonium Glycyrrhizinate on Lipopolysaccharide-Induced Acute Lung Injury in Mice through Regulating Nuclear Factor-Kappa B Signaling Pathway

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Xiaoying Huang ◽  
Jiangfeng Tang ◽  
Hui Cai ◽  
Yi Pan ◽  
Yicheng He ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Signaling Pathway ◽  
Interleukin 1 ◽  
Intratracheal Instillation ◽  
Weight Ratio ◽  
Dry Weight ◽  
Inflammatory Cells ◽  
Lavage Fluid ◽  
Therapeutic Mechanism

The present study aimed to investigate the therapeutic effect of monoammonium glycyrrhizinate (MAG) on lipopolysaccharide- (LPS-) induced acute lung injury (ALI) in mice and possible mechanism. Acute lung injury was induced in BALB/c mice by intratracheal instillation of LPS, and MAG was injected intraperitoneally 1 h prior to LPS administration. After ALI, the histopathology of lungs, lung wet/dry weight ratio, protein concentration, and inflammatory cells in the bronchoalveolar lavage fluid (BALF) were determined. The levels of tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β) in the BALF were measured by ELISA. The activation of NF-κB p65 and IκB-αof lung homogenate was detected by Western blot. Pretreatment with MAG attenuated lung histopathological damage induced by LPS and decreased lung wet/dry weight ratio and the concentrations of protein in BALF. At the same time, MAG reduced the number of inflammatory cells in lung and inhibited the production of TNF-αand IL-1βin BALF. Furthermore, we demonstrated that MAG suppressed activation of NF-κB signaling pathway induced by LPS in lung. The results suggested that the therapeutic mechanism of MAG on ALI may be attributed to the inhibition of NF-κB signaling pathway. Monoammonium glycyrrhizinate may be a potential therapeutic reagent for ALI.

Redistribution of pulmonary EC-SOD after exposure to asbestos

2004 ◽  
Vol 97 (5) ◽  
pp. 2006-2013 ◽  
Author(s):  
Roderick J. Tan ◽  
Cheryl L. Fattman ◽  
Simon C. Watkins ◽  
Tim D. Oury
Keyword(s):  
Extracellular Matrix ◽  
Lung Injury ◽  
Asbestos Exposure ◽  
Intratracheal Instillation ◽  
Inflammatory Cells ◽  
Lung Parenchyma ◽  
Lavage Fluid ◽  
Binding Domain ◽  
Heparin Binding ◽  
Heparin Binding Domain

Inhalation of asbestos fibers leads to interstitial lung disease (asbestosis) characterized by inflammation and fibrosis. The pathogenesis of asbestosis is not fully understood, but reactive oxygen species are thought to play a central role. Extracellular superoxide dismutase (EC-SOD) is an antioxidant enzyme that protects the lung in a bleomycin-induced pulmonary fibrosis model, but its role has not been studied in asbestos-mediated disease. EC-SOD is found in high levels in the extracellular matrix of lung alveoli because of its positively charged heparin-binding domain. Proteolytic removal of this domain results in clearance of EC-SOD from the matrix of tissues. We treated wild-type C57BL/6 mice with 0.1 mg of crocidolite asbestos by intratracheal instillation and euthanized them 24 h later. Compared with saline- or titanium dioxide-treated control mice, bronchoalveolar lavage fluid (BALF) from asbestos-treated mice contained significantly higher total protein levels and increased numbers of inflammatory cells, predominantly neutrophils, indicating acute lung injury in response to asbestos. Decreased EC-SOD protein and activity were found in the lungs of asbestos-treated mice, whereas more EC-SOD was found in the BALF of these mice. The EC-SOD in the BALF was predominantly in the proteolyzed form, which lacks the heparin-binding domain. This redistribution of EC-SOD correlated with development of fibrosis 14 days after asbestos exposure. These data suggest that asbestos injury leads to enhanced proteolysis and clearance of EC-SOD from lung parenchyma into the air spaces. The depletion of EC-SOD from the extracellular matrix may increase susceptibility of the lung to oxidative stress during asbestos-mediated lung injury.

Effect of exogenous surfactant instillation on experimental acute lung injury

1989 ◽  
Vol 66 (4) ◽  
pp. 1846-1851 ◽  
Author(s):  
J. D. Harris ◽  
F. Jackson ◽  
M. A. Moxley ◽  
W. J. Longmore
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Surface Activity ◽  
Pulmonary Surfactant ◽  
Exogenous Surfactant ◽  
Protein Ratio ◽  
Surfactant Replacement ◽  
Lung Injury Model ◽  
Surfactant Phospholipids ◽  
The Individual

Pulmonary surfactant replacement has previously been shown to be effective in the human neonatal respiratory distress syndrome. The value of surfactant replacement in models of acute lung injury other than quantitative surfactant deficiency states is, however, uncertain. In this study an acute lung injury model using rats with chronic indwelling arterial catheters, injured with N-nitroso-N-methylurethane (NNNMU), has been developed. The NNNMU injury was found to produce hypoxia, increased mortality, an alveolitis, and alterations in the pulmonary surfactant system. Alterations of surfactant obtained by bronchoalveolar lavage included a reduction in the phospholipid-to-protein ratio, reduced surface activity, and alterations in the relative percentages of the individual phospholipids compared with controls. Treatment of the NNNMU-injured rats with instilled exogenous surfactant (Survanta) improved oxygenation; reduced mortality to control values; and returned the surfactant phospholipid-to-protein ratio, surface activity, and, with the exception of phosphatidylglycerol, the relative percentages of individual surfactant phospholipids to control values.

scholarly journals Alveolar Type II Cells and Pulmonary Surfactant in COVID-19 Era

2021 ◽  
pp. S195-S208
Author(s):  
A CALKOVSKA ◽  
M KOLOMAZNIK ◽  
V CALKOVSKY
Keyword(s):  
Pulmonary Surfactant ◽  
Lung Mechanics ◽  
Exogenous Surfactant ◽  
Lung Edema ◽  
Target Cells ◽  
Alveolar Type ◽  
Respiratory Pathogens ◽  
Type Ii ◽  
Novel Coronavirus

In this review, we discuss the role of pulmonary surfactant in the host defense against respiratory pathogens, including novel coronavirus SARS-CoV-2. In the lower respiratory system, the virus uses angiotensin-converting enzyme 2 (ACE2) receptor in conjunction with serine protease TMPRSS2, expressed by alveolar type II (ATII) cells as one of the SARS-CoV-2 target cells, to enter. ATII cells are the main source of surfactant. After their infection and the resulting damage, the consequences may be severe and may include injury to the alveolar-capillary barrier, lung edema, inflammation, ineffective gas exchange, impaired lung mechanics and reduced oxygenation, which resembles acute respiratory distress syndrome (ARDS) of other etiology. The aim of this review is to highlight the key role of ATII cells and reduced surfactant in the pathogenesis of the respiratory form of COVID-19 and to emphasize the rational basis for exogenous surfactant therapy in COVID-19 ARDS patients.

scholarly journals Protective Effects of Li-Fei-Xiao-Yan Prescription on Lipopolysaccharide-Induced Acute Lung Injury via Inhibition of Oxidative Stress and the TLR4/NF-κB Pathway

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Lie-Qiang Xu ◽  
Xiu-Ting Yu ◽  
Shu-Hua Gui ◽  
Jian-hui Xie ◽  
Xiu-Fen Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Therapeutic Agent ◽  
Inflammatory Responses ◽  
Intratracheal Instillation ◽  
Inflammatory Cells ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
Lung Histopathology

Li-Fei-Xiao-Yan prescription (LFXY) has been clinically used in China to treat inflammatory and infectious diseases including inflammatory lung diseases. The present study was aimed at evaluating the potential therapeutic effects and potential mechanisms of LFXY in a murine model of lipopolysaccharide- (LPS-) induced acute lung injury (ALI). In this study, the mice were orally pretreated with LFXY or dexamethasone (positive drug) before the intratracheal instillation of LPS. Our data indicated that pretreatment with LFXY enhanced the survival rate of ALI mice, reversed pulmonary edema and permeability, improved LPS-induced lung histopathology impairment, suppressed the excessive inflammatory responsesviadecreasing the expression of proinflammatory cytokines (TNF-α, IL-1β, and IL-6) and chemokine (MIP-2) and inhibiting inflammatory cells migration, and repressed oxidative stress through the inhibition of MPO and MDA contents and the upregulation of antioxidants (SOD and GSH) activities. Mechanistically, treatment with LFXY significantly prevented LPS-induced TLR4 expression and NF-κB (p65) phosphorylation. Overall, the present study suggests that LFXY protected mice from acute lung injury induced by LPSviainhibition of TLR4/NF-κB p65 activation and upregulation of antioxidative enzymes and it may be a potential preventive and therapeutic agent for ALI in the clinical setting.

Development of O2 tolerance in rabbits with no increase in antioxidant enzymes

1989 ◽  
Vol 66 (4) ◽  
pp. 1679-1684 ◽  
Author(s):  
R. R. Baker ◽  
B. A. Holm ◽  
P. C. Panus ◽  
S. Matalon
Keyword(s):  
Pulmonary Surfactant ◽  
Respiratory Acidosis ◽  
Exogenous Surfactant ◽  
Alveolar Type ◽  
Alveolar Epithelial ◽  
Type Ii Pneumocytes ◽  
Hyperoxic Exposure ◽  
Alveolar Permeability ◽  
Alveolar Epithelial Injury ◽  
Specific Activities

Instillation of exogenous surfactant into rabbits exposed to 100% O2 increases survival time and decreases alveolar epithelial injury. In this study we investigated whether rabbits with increased levels of endogenous pulmonary surfactant are more resistant to hyperoxia. Rabbits were exposed to 100% O2 for 64 h and then returned to room air for 8 days (preexposed). At this time, they had normal gas exchange and alveolar permeability to solute and increased levels of lavageable alveolar phospholipids compared with control rabbits breathing air (26 +/- 2 vs. 12 +/- 2 mumol/kg). Preexposed rabbits survived significantly longer than control rabbits when reexposed to 100% O2 (166 +/- 24 vs. 80 +/- 6 h; n = 7; P less than 0.05) and had significantly higher values of total lavageable phospholipids after 72 h in 100% O2 (15 +/- 2 vs. 5 +/- 2 mumol/kg). Controls developed arterial hypoxemia after 72 h in 100% O2. On the other hand, preexposed rabbits maintained arterial PO2 values greater than 100 Torr throughout the hyperoxic exposure and developed progressive respiratory acidosis. Specific activities of CuZn and Mn superoxide dismutase, catalase, and glutathione peroxidase in lung homogenates and isolated alveolar type II pneumocytes of preexposed rabbits were unchanged from those of controls before O2 reexposure and after 72 h in 100% O2. We concluded that 1) increases in pulmonary antioxidant enzyme specific activities are not necessary for the development of O2 tolerance in rabbits and 2) pulmonary surfactant may play a role in O2 adaptation.

Myeloperoxidase deficiency enhances inflammation after allogeneic marrow transplantation

2004 ◽  
Vol 287 (4) ◽  
pp. L706-L714 ◽  
Author(s):  
Carlos Milla ◽  
Shuxia Yang ◽  
David N. Cornfield ◽  
Marie-Luise Brennan ◽  
Stanley L. Hazen ◽  
...  
Keyword(s):  
Lung Injury ◽  
Marrow Transplantation ◽  
Inflammatory Responses ◽  
Inflammatory Cells ◽  
Alveolar Type ◽  
Monocyte Chemoattractant Protein 1 ◽  
Alveolar Epithelial ◽  
Nitrative Stress ◽  
Lung Dysfunction ◽  
Allogeneic Marrow Transplantation

Myeloperoxidase (MPO)-derived oxidants participate in the respiratory antimicrobial defense system but are also implicated in oxidant-mediated acute lung injury. We hypothesized that MPO contributes to lung injury commonly observed after bone marrow transplantation (BMT). MPO-sufficient (MPO+/+) and -deficient (MPO−/−) mice were given cyclophosphamide and lethally irradiated followed by infusion of inflammation-inducing donor spleen T cells at time of BMT. Despite suppressed generation of nitrative stress, MPO−/− recipient mice unexpectedly exhibited accelerated weight loss and increased markers of lung dysfunction compared with MPO+/+ mice. The increased lung injury during MPO deficiency was a result of donor T cell-dependent inflammatory responses because bronchoalveolar lavage fluids (BALF) from MPO−/− mice contained increased numbers of inflammatory cells and higher levels of the proinflammatory cytokine TNF-α and the monocyte chemoattractant protein-1 compared with wild-type mice. Enhanced inflammation in MPO−/− mice was associated with suppressed apoptosis of BALF inflammatory cells. The inflammatory process in MPO−/− recipients was also associated with enhanced necrosis of freshly isolated alveolar type II cells, critical for preventing capillary leak. We conclude that suppressed MPO-derived oxidative/nitrative stress is associated with enhanced lung inflammation and persistent alveolar epithelial injury.

Intratracheal instillation of alveolar type II cells enhances recovery from acute lung injury in rats

2018 ◽  
Vol 37 (6) ◽  
pp. 782-791 ◽  
Author(s):  
Raquel Guillamat-Prats ◽  
Ferranda Puig ◽  
Marta Camprubí-Rimblas ◽  
Raquel Herrero ◽  
Anna Serrano-Mollar ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Intratracheal Instillation ◽  
Alveolar Type ◽  
Type Ii Cells ◽  
Type Ii ◽  
Alveolar Type Ii Cells

scholarly journals The Protective Effects of the Supercritical-Carbon Dioxide Fluid Extract ofChrysanthemum indicumagainst Lipopolysaccharide-Induced Acute Lung Injury in Mice via Modulating Toll-Like Receptor 4 Signaling Pathway

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Xiao-Li Wu ◽  
Xue-Xuan Feng ◽  
Chu-Wen Li ◽  
Xiao-Jun Zhang ◽  
Zhi-Wei Chen ◽  
...  
Keyword(s):  
Carbon Dioxide ◽  
Acute Lung Injury ◽  
Supercritical Carbon Dioxide ◽  
Lung Injury ◽  
Intratracheal Instillation ◽  
Inflammatory Cells ◽  
Therapeutic Drug ◽  
Protective Effects ◽  
Preventive Action ◽  
Supercritical Carbon

The supercritical-carbon dioxide fluid extract ofChrysanthemum indicumLinné. (CFE) has been demonstrated to be effective in suppressing inflammation. The aim of this study is to investigate the preventive action and underlying mechanisms of CFE on acute lung injury (ALI) induced by lipopolysaccharide (LPS) in mice. ALI was induced by intratracheal instillation of LPS into lung, and dexamethasone was used as a positive control. Results revealed that pretreatment with CFE abated LPS-induced lung histopathologic changes, reduced the wet/dry ratio and proinflammatory cytokines productions (TNF-α, IL-1β, and IL-6), inhibited inflammatory cells migrations and protein leakages, suppressed the levels of MPO and MDA, and upregulated the abilities of antioxidative enzymes (SOD, CAT, and GPx). Furthermore, the pretreatment with CFE downregulated the activations of NF-κB and the expressions of TLR4/MyD88. These results suggested that CFE exerted potential protective effects against LPS-induced ALI in mice and was a potential therapeutic drug for ALI. Its mechanisms were at least partially associated with the modulations of TLR4 signaling pathways.

Matrix metalloproteinase and elastase activities in LPS-induced acute lung injury in guinea pigs

1994 ◽  
Vol 266 (3) ◽  
pp. L209-L216 ◽  
Author(s):  
M. P. D'Ortho ◽  
P. H. Jarreau ◽  
C. Delacourt ◽  
I. Macquin-Mavier ◽  
M. Levame ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Guinea Pigs ◽  
Culture Media ◽  
Proteolytic Enzymes ◽  
Intratracheal Instillation ◽  
Inflammatory Cells ◽  
Polymorphonuclear Neutrophils ◽  
Control Group ◽  
Gelatinase Activity

Matrix metalloproteinases (MMPs) and elastase are proteolytic enzymes specifically directed against extracellular matrix (ECM) components. They are secreted by inflammatory cells and may consequently contribute to the lesions of the ECM observed during acute pulmonary edema. We therefore evaluated the MMP and elastase activities, which are secreted by cultured alveolar macrophages (AMACs) and polymorphonuclear neutrophils (PMNs) and present in the bronchoalveolar lavage (BAL) fluid in a guinea pig model of acute lung injury induced by intratracheal instillation of lipopolysaccharide (LPS). The control group was given 0.9% NaCl. 24 h after instillation, a BAL was performed, the BAL fluid was separated from the cells by centrifugation, and AMACs and PMNs were separately cultured for 24 h. In BAL fluid from LPS-treated guinea pigs, we found 1) an increase in free gelatinase activity, tested on [3H]gelatin (0.7 +/- 0.2 micrograms.200 microliters BAL fluid-1.48 h-1 vs. 0.2 +/- 0.1 in controls, P < 0.05), and 2) increased total gelatinase activities, as assessed by zymography. The molecular masses of the major gelatinase species found in BAL fluid by zymography were 92 and 68 kDa. The 92-kDa gelatinase was secreted by both AMACs and PMNs, as demonstrated by zymography of their respective culture media. When tested on [3H]elastin, the elastase activity of BAL fluid of LPS-treated animals exhibited no increase, but when tested on a synthetic peptidic substrate [N-succinyl-(L-alanine)3-p-nitro anilide (SLAPN)], increased elastase-like activity was observed (from 17 +/- 4 nmol of SLAPN.200 microliters BAL fluid-1.24 h-1 in control group to 34 +/- 8 in LPS group, P < 0.05). This increase was attributable to the activity of a metalloendopeptidase that was inhibited by the metal chelator EDTA but not by the specific tissue inhibitor of MMPs.

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