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.

Stabilizing mast cells improves acute lung injury after orthotopic liver transplantation via promotion of apoptosis in polymorphonuclear neutrophils

2020 ◽  
Author(s):  
Chaojin Chen ◽  
Zheng Zhang ◽  
Fang Tan ◽  
Fanbing Meng ◽  
Lifei Lai ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Acute Lung Injury ◽  
Mast Cells ◽  
Lung Injury ◽  
Orthotopic Liver Transplantation ◽  
Inflammatory Cells ◽  
Pulmonary Complications ◽  
Polymorphonuclear Neutrophils ◽  
Inflammatory Factor ◽  
Tnf Α

Aims: Postoperative pulmonary complications including acute lung injury (ALI) and acute respiratory distress syndrome have contributed to the mortality and morbidity of orthotopic liver transplantation (OLT) with unclear mechanisms. Mast cells (MCs) and polymorphonuclear neutrophils (PMNs) are the main inflammatory cells and participants in the process of ALI. The present study was designed to investigate the role of MCs and PMNs and their potential relation to ALI following OLT. Main Methods: Rat orthotopic autologous liver transplantation (OALT) model was designed to determine lung injury at different time points after liver reperfusion. We also evaluated the function of MCs and the effect of TNF-α and tryptase on ALI and PMN apoptosis in rats subjected to OALT. Histological scores and inflammatory factor levels as well as PMN apoptosis were measured. Key findings: Rats suffered from ALI after OALT, which was demonstrated with collapse of pulmonary architecture, pulmonary edema, and infiltration of inflammatory cells in alveolar and interstitial spaces, as well as increased levels of pro-inflammatory cytokines. ALI maximized at 8 h after OALT. However, PMN apoptosis lagged behind the pulmonary injury and maximized at 16 h after OALT, when the acute inflammation resolution initiated. MC stabilization, and tryptase and TNF-α inhibitors could significantly decrease the lung pathophysiologic scores accompanied with an increase in PMN apoptosis. Significance: ALI after OLT was associated with MC activation and PMN apoptosis. The ALI progression might be affected by delayed PMN apoptosis, which was related to MC activation. Induction of PMN apoptosis might alleviate ALI after OALT.

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.

Expression of p38 MAPK in Acute Lung Injury Induced by LPS in Mice

2014 ◽  
Vol 522-524 ◽  
pp. 332-336 ◽  
Author(s):  
Kai Xiu Qin ◽  
Yong Wang ◽  
Hua Gang Jian
Keyword(s):  
Endothelial Cells ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
P38 Mapk ◽  
Inflammatory Cells ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Control Group ◽  
Mitogen Activated Protein ◽  
Set Up

Objective To investigate the expression and roles of p38 mitogen-activated protein kinase (p38 MAPK) in LPS-induced acute lung injury (ALI) in mice. Methods The ALI mice models were set up by intraperineal injection of lipopolysaccharide (LPS). The expressions of p38 MAPK in lung tissues were detected by immunohistochemistry and Western-blot. Results The positive expressions of p38 MAPK distribute mainly in infiltrative inflammatory cells, epithelial cells and endothelial cells. And the level of expression of phosphated p38 MAPK in ALI group were higher obviously than that in the control group, and it reached a peak after two hours. Conclusion p38 MAPK signaling pathway was triggered by ALI induced by endotoxin.

scholarly journals The Activation of Macrophage and Upregulation of CD40 Costimulatory Molecule in Lipopolysaccharide-Induced Acute Lung Injury

2008 ◽  
Vol 2008 ◽  
pp. 1-6 ◽  
Author(s):  
Liang Dong ◽  
Shujuan Wang ◽  
Ming Chen ◽  
Hongjia Li ◽  
Wenxiang Bi
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Costimulatory Molecule ◽  
Inflammatory Cells ◽  
Lavage Fluid ◽  
Vital Role ◽  
Control Group ◽  
Toll Like Receptor 4 ◽  
Activated Macrophage ◽  
Lps Treatment

To study the activation of macrophage and upregulation of costimulatory molecule of CD40 in lipopolysaccharide- (LPS-) induced acute lung injury (ALI) model, and to investigate the pathogenecy of ALI, mice were randomly divided into two groups. ALI model was created by injecting 0.2 mg/kg LPS in phosphate saline (PBS) in trachea. The pathologic changes of mice lungs were observed by HE staining at 24 and 48 hours after LPS treatment, then the alveolar septum damage, abnormal contraction, alveolar space hyperemia, and neutrophils or other inflammatory cells infiltration in the LPS group, but not in the control group, were observed. The expression of CD40 mRNA and CD40 protein molecules were higher in LPS group as compared to the control group by Northern blot and flow cytometry, respectively. Expression of Toll-like receptor-4 (TLR4) in activated macrophage (AM) was higher in LPS group as compared to the control group by RT-PCR. The activation of NF-B binding to NF-B consensus oligos increased in LPS group by EMSA in macrophage. The concentrations of TNF-, MIP-2, and IL-1 cytokines from bronchoalveolar lavage fluid (BALF) were increased significantly in LPS group as compared to the control group by ELISA. The activation of AM and upregulation of costimulatory molecule CD40 induced all kinds of inflammatory cytokines releasing, then led to ALI. Therefore, both of them played vital role in the process of development of ALI.

Prevention of interleukin 2-induced acute lung injury in guinea pigs by pentoxifylline

1989 ◽  
Vol 67 (6) ◽  
pp. 2432-2437 ◽  
Author(s):  
A. Ishizaka ◽  
J. R. Hatherill ◽  
H. Harada ◽  
M. Yonemaru ◽  
H. Hoffmann ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Guinea Pigs ◽  
Interleukin 2 ◽  
Weight Ratio ◽  
Saline Control ◽  
Control Group ◽  
Lung Water ◽  
Lung Weight ◽  
Cell Counts

We administered recombinant human interleukin 2 (IL-2) to guinea pigs to investigate whether IL-2 would cause acute lung injury. In addition, we examined the effects of pentoxifylline (PTXF) on IL-2-induced acute lung injury. Three groups of animals were studied over a period of 8 h. The saline control group was injected intravenously with 2 ml of pyrogen-free saline; the IL-2 group was injected intravenously with 4 X 10(6) U/kg recombinant IL-2; and the IL-2-PTXF group was injected with a 20-mg/kg bolus of PTXF followed by a continuous infusion (6 mg.kg-1.h-1) started 60 min before injection of 4 X 10(6) U/kg IL-2. Lung water (wet-to-dry lung weight ratio), the concentration ratios of 125I-albumin in bronchoalveolar lavage (BAL) fluid and lung tissue compared with plasma (125I-albumin BAL-to-plasma, 125I-albumin lung-to-plasma), and cell counts in BAL fluid were examined. An intravenous injection of IL-2 caused an increased lung water (P less than 0.01), an increased 125I-albumin lung-to-plasma ratio (P less than 0.05), and a significant increase in the absolute number of neutrophils, lymphocytes, and macrophages in BAL fluid compared with the saline control. In contrast, the PTXF-pretreated group did not demonstrate IL-2-induced acute lung injury (lung water, 125I-albumin lung-to-plasma) or increased accumulation of neutrophils, lymphocytes, and macrophages in the BAL. These data suggest a possible role for PTXF in attenuating the side effects of IL-2.

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.

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.

Dual roles of neutrophils in the pathogenesis of acute lung injury induced by intratracheal instillation of live bacteria in guinea pigs

1994 ◽  
Vol 1 ◽  
pp. 410
Author(s):  
M. Kanazawa ◽  
T. Terashima ◽  
K. Sayama ◽  
S. Tasaka ◽  
K. Soejima ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Guinea Pigs ◽  
Intratracheal Instillation ◽  
Dual Roles ◽  
Live Bacteria

Metalloproteinase and growth factor interactions: do they play a role in pulmonary fibrosis?

2002 ◽  
Vol 283 (1) ◽  
pp. L1-L11 ◽  
Author(s):  
Margaret K. Winkler ◽  
John L. Fowlkes
Keyword(s):  
Acute Lung Injury ◽  
Growth Factors ◽  
Growth Factor ◽  
Pulmonary Fibrosis ◽  
Lung Injury ◽  
Transforming Growth Factor ◽  
Interstitial Fibrosis ◽  
Inflammatory Cells ◽  
Transforming Growth Factor Β ◽  
Target Cells

Chronic lung disease due to interstitial fibrosis can be a consequence of acute lung injury and inflammation. The inflammatory response is mediated through the migration of inflammatory cells, actions of proinflammatory cytokines, and the secretion of matrix-degrading proteinases. After the initial inflammatory insult, successful healing of the lung may occur, or alternatively, dysregulated tissue repair can result in scarring and fibrosis. On the basis of recent insights into the mechanisms underlying acute lung injury and its long-term consequences, data suggest that proteinases, such as the matrix metalloproteinases (MMPs), may not only be involved in the breakdown and remodeling that occurs during the injury but may also cause the release of growth factors and cytokines known to influence growth and differentiation of target cells within the lung. Through the release of and activation of fibrosis-promoting cytokines and growth factors such as transforming growth factor-β1, tumor necrosis factor-α, and insulin-like growth factors by MMPs, we propose that these metalloproteinases may be integral to the initiation and progression of pulmonary fibrosis.

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