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

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.

Attenuation of acute lung injury and oxygen radical production by the 21-aminosteroid, U-78518F

1993 ◽  
Vol 74 (5) ◽  
pp. 2155-2160 ◽  
Author(s):  
T. Tanigaki ◽  
Y. Suzuki ◽  
D. Heimer ◽  
H. H. Sussman ◽  
W. G. Ross ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Phorbol Myristate Acetate ◽  
Guinea Pigs ◽  
Oxygen Radical ◽  
Myristate Acetate ◽  
E Coli ◽  
Radical Production ◽  
Oxygen Radical Production

Oxygen radicals play an important role in the mechanism of acute lung injury. The 21-aminosteroid lazaroid, U-78518F, is a potent antioxidant. We examined the effect of intravenous U-78518F on acute lung injury in septic guinea pigs over 8 h. The experimental groups (n = 6) were 1) saline control, 2) Escherichia coli (2 x 10(9)/kg i.v.), 3) pretreatment (U-78518F 5 mg/kg bolus + 1 mg.kg-1 x h-1, 15 min before E. coli injection), and 4) posttreatment (U-78518F 30 min after E. coli injection). We measured wet-to-dry weight ratio (W/D) as an index of pulmonary edema and concentration ratios of 125I-labeled albumin in lung tissue and bronchoalveolar lavage fluid compared with plasma (L/P and BAL/P, respectively) as indexes of lung protein fluxes. In septic guinea pigs, pretreatment with U-78518F attenuated W/D, L/P, and BAL/P and posttreatment attenuated W/D and BAL/P (P < 0.05 for each). Furthermore, we studied the effect of U-78518F on human neutrophil oxygen radical production (ORP) by using flow cytometry to assess intracellular ORP and lucigenin-dependent chemiluminescence to assess extracellular ORP. Neutrophils (5 x 10(5) were stimulated with 0.5 micrograms/ml of phorbol myristate acetate. With flow cytometry, we measured intracellular ORP, cross-sectional cell area, and degranulation in neutrophils. U-78518F (minimum concn 1.0 microM) decreased intracellular ORP (n = 4; P < 0.05) when the dihydrorhodamine 123 assay was used. U-78518F (minimum concn 1.0 microM) inhibited phorbol myristate acetate-induced neutrophil chemiluminescence (n = 4; P < 0.05).

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.

scholarly journals Endotoxin-induced acute lung injury in guinea pigs.

Ensho ◽  
1992 ◽  
Vol 12 (6) ◽  
pp. 525-528
Author(s):  
Yukio Suzuki ◽  
Akitoshi Ishizaka ◽  
Hirofumi Fujita ◽  
Minoru Kanazawa ◽  
Takeo Kawashiro ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Guinea Pigs

scholarly journals Biocompatible N-acetyl-nanoconstruct alleviates lipopolysaccharide-induced acute lung injury in vivo

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Seongchan Kim ◽  
Shin Young Kim ◽  
Seung Joon Rho ◽  
Seung Hoon Kim ◽  
So Hyang Song ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Intratracheal Instillation ◽  
Sprague Dawley ◽  
In Vivo Experiments ◽  
Anti Inflammatory

AbstractOxidative stress plays important roles in inflammatory responses during acute lung injury (ALI). Recently, nanoconstruct (Nano)-based drug-delivery systems have shown promise in many models of inflammation. In this study, we evaluated the anti-inflammatory effects of N-acetylcysteine (NAC) loaded in a biocompatible Nano using a rat model of ALI. We synthesized a Nano with a good NAC-releasing capacity using porous silica Nano, which was used to produce Nano/NAC complexes. For in vivo experiments, Sprague–Dawley rats were intraperitoneally administered NAC or Nano/NAC 30 min after intratracheal instillation of lipopolysaccharide. After 6 h, bronchoalveolar lavage fluids and lung tissues were collected. The anti-oxidative effect of the Nano/NAC complex was confirmed by demonstrating reduced levels of reactive oxygen species after treatment with the Nano/NAC in vitro. In vivo experiments also showed that the Nano/NAC treatment may protect against LPS‐induced ALI thorough anti‐oxidative and anti‐inflammatory effects, which may be attributed to the inactivation of the NF‐κB and MAPK pathways. In addition, the effects of Nano/NAC treatment were shown to be superior to those of NAC alone. We suggest the therapeutic potential of Nano/NAC treatment as an anti‐inflammatory agent against ALI. Furthermore, our study can provide basic data for developing nanotechnology-based pharmacotherapeutics for ALI.

scholarly journals Attenuation of half sulfur mustard gas‐induced acute lung injury in guinea pigs by antioxidant liposomes

2007 ◽  
Vol 21 (5) ◽  
Author(s):  
Shyamali Mukherjee ◽  
William L Stone ◽  
Hongsong Yang ◽  
Milton Smith ◽  
Salil K Das
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Guinea Pigs ◽  
Sulfur Mustard ◽  
Mustard Gas

scholarly journals Double-hit mouse model of cigarette smoke priming for acute lung injury

2017 ◽  
Vol 312 (1) ◽  
pp. L56-L67 ◽  
Author(s):  
Pavlo Sakhatskyy ◽  
Zhengke Wang ◽  
Diana Borgas ◽  
Joanne Lomas-Neira ◽  
Yaping Chen ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Mouse Model ◽  
Strain Difference ◽  
Intratracheal Instillation ◽  
Epidemiological Studies ◽  
Lung Edema ◽  
Key Features ◽  
Double Hit ◽  
Akr Mice

Epidemiological studies indicate that cigarette smoking (CS) increases the risk and severity of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). The mechanism is not understood, at least in part because of lack of animal models that reproduce the key features of the CS priming process. In this study, using two strains of mice, we characterized a double-hit mouse model of ALI induced by CS priming of injury caused by lipopolysaccharide (LPS). C57BL/6 and AKR mice were preexposed to CS briefly (3 h) or subacutely (3 wk) before intratracheal instillation of LPS and ALI was assessed 18 h after LPS administration by measuring lung static compliance, lung edema, vascular permeability, inflammation, and alveolar apoptosis. We found that as little as 3 h of exposure to CS enhanced LPS-induced ALI in both strains of mice. Similar exacerbating effects were observed after 3 wk of preexposure to CS. However, there was a strain difference in susceptibility to CS priming for ALI, with a greater effect in AKR mice. The key features we observed suggest that 3 wk of CS preexposure of AKR mice is a reproducible, clinically relevant animal model that is useful for studying mechanisms and treatment of CS priming for a second-hit-induced ALI. Our data also support the concept that increased susceptibility to ALI/ARDS is an important adverse health consequence of CS exposure that needs to be taken into consideration when treating critically ill individuals.

Early Post-Treatment with Pentoxifylline or Dibutyryl cAMP AttenuatesEscherichia coli-induced Acute Lung Injury in Guinea Pigs

1991 ◽  
Vol 143 (2) ◽  
pp. 289-293 ◽  
Author(s):  
Hans Hoffmann ◽  
John R. Hatherill ◽  
Jeffrey Crowley ◽  
Hiromasa Harada ◽  
Makoto Yonemaru ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Guinea Pigs ◽  
Post Treatment ◽  
Dibutyryl Camp

Adrenomedullin ameliorates lipopolysaccharide-induced acute lung injury in rats

2007 ◽  
Vol 293 (2) ◽  
pp. L446-L452 ◽  
Author(s):  
Takefumi Itoh ◽  
Hiroaki Obata ◽  
Shinsuke Murakami ◽  
Kaoru Hamada ◽  
Kenji Kangawa ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Bronchoalveolar Lavage ◽  
Total Protein ◽  
Intratracheal Instillation ◽  
Weight Ratio ◽  
Dry Weight ◽  
Alveolar Wall ◽  
Protective Effects ◽  
Tnf Α

Adrenomedullin (AM), an endogenous peptide, has been shown to have a variety of protective effects on the cardiovascular system. However, the effect of AM on acute lung injury remains unknown. Accordingly, we investigated whether AM infusion ameliorates lipopolysaccharide (LPS)-induced acute lung injury in rats. Rats were randomized to receive continuous intravenous infusion of AM (0.1 μg·kg−1·min−1) or vehicle through a microosmotic pump. The animals were intratracheally injected with either LPS (1 mg/kg) or saline. At 6 and 18 h after intratracheal instillation, we performed histological examination and bronchoalveolar lavage and assessed the lung wet/dry weight ratio as an index of acute lung injury. Then we measured the numbers of total cells and neutrophils and the levels of tumor necrosis factor (TNF)-α and cytokine-induced neutrophil chemoattractant (CINC) in bronchoalveolar lavage fluid (BALF). In addition, we evaluated BALF total protein and albumin levels as indexes of lung permeability. LPS instillation caused severe acute lung injury, as indicated by the histological findings and the lung wet/dry weight ratio. However, AM infusion attenuated these LPS-induced abnormalities. AM decreased the numbers of total cells and neutrophils and the levels of TNF-α and CINC in BALF. AM also reduced BALF total protein and albumin levels. In addition, AM significantly suppressed apoptosis of alveolar wall cells as indicated by cleaved caspase-3 staining. In conclusion, continuous infusion of AM ameliorated LPS-induced acute lung injury in rats. This beneficial effect of AM on acute lung injury may be mediated by inhibition of inflammation, hyperpermeability, and alveolar wall cell apoptosis.

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