scholarly journals Pulmonary surfactant synthesis after unilateral lung injury in mice

2014 ◽  
Vol 116 (2) ◽  
pp. 210-215 ◽  
Author(s):  
Giulia Lamonica ◽  
Maria Amigoni ◽  
Luca Vedovelli ◽  
Vanessa Zambelli ◽  
Margherita Scanziani ◽  
...  

Aspiration pneumonitis can lead to alveolar surfactant dysfunction. We employed a murine model of unilateral aspiration to compare surfactant synthesis in the injured (I) and noninjured (NI) contralateral lung. Mice were instilled with hydrochloric acid in the right bronchus and, after 18 h, an intraperitoneal dose of deuterated water was administered as precursor of disaturated phosphatidylcholine (DSPC)-palmitate. Selected bronchoalveolar lavage fluid (BALF) was collected at scheduled time points and lungs were removed. We measured DSPC-palmitate synthesis in lung tissue and secretion in BALF by gas chromatography-isotope ratio mass spectrometry, together with total proteins and myeloperoxidase activity (MPO) by spectrophotometry. BALF total proteins and MPO were significantly increased in the I lungs compared with NI and naïve control lungs. The DSPC pool size was significantly lower in the BALF of the I lungs compared with naïve controls. DSPC synthesis was accelerated in the I and NI lungs. DSPC secretion of the I lungs was similar to their respective naïve controls, and it was markedly lower compared with their respective NI contralateral lungs. DSPC synthesis and secretion were faster, especially in the NI lungs, compared with naïve control lungs, as a possible compensatory mechanism due to a cross-talk between the lungs triggered by inflammation, hyperventilation, and/or undetermined type II cell reaction to the injury.

2000 ◽  
Vol 279 (1) ◽  
pp. L75-L80 ◽  
Author(s):  
Young M. Lee ◽  
Brooks M. Hybertson ◽  
Hyun G. Cho ◽  
Lance S. Terada ◽  
Okyong Cho ◽  
...  

Lung lavage fluid of patients with acute lung injury (ALI) has increased levels of interleukin-1 (IL-1) and neutrophils, but their relationship to the lung leak that characterizes these patients is unclear. To address this concern, we investigated the role of the neutrophil agonist platelet-activating factor [1- O-alkyl-2-acetyl- sn-glycero-3-phosphocholine (PAF)] in the development of the acute neutrophil-dependent lung leak that is induced by giving IL-1 intratracheally to rats. We found that PAF acetyltransferase and PAF activities increased in lungs of rats given IL-1 intratracheally compared with lungs of sham-treated rats given saline intratracheally. The participation of PAF in the development of lung leak and lung neutrophil accumulation after IL-1 administration was suggested when treatment with WEB-2086, a commonly used PAF-receptor antagonist, decreased lung leak, lung myeloperoxidase activity, and lung lavage fluid neutrophil increases in rats given IL-1 intratracheally. Additionally, neutrophils recovered from the lung lavage fluid of rats given IL-1 intratracheally reduced more nitro blue tetrazolium (NBT) in vitro than neutrophils recovered from control rats or rats that had been given WEB-2086 and then IL-1. Histological examination indicated that the endothelial cell-neutrophil interfaces of cerium chloride-stained lung sections of rats given IL-1 contained increased cerium perhydroxide (the reaction product of cerium chloride with hydrogen peroxide) compared with lungs of control rats or rats treated with WEB-2086 and then given IL-1 intratracheally. These in vivo findings were supported by parallel findings showing that WEB-2086 treatment decreased neutrophil adhesion to IL-1-treated cultured endothelial cells in vitro. We concluded that PAF contributes to neutrophil recruitment and neutrophil activation in lungs of rats given IL-1 intratracheally.


1990 ◽  
Vol 259 (2) ◽  
pp. H518-H524 ◽  
Author(s):  
R. M. Jackson ◽  
C. F. Veal

Reexpansion pulmonary edema (RPE) parallels reperfusion (reoxygenation) injuries in other organs in that hypoxic and hypoperfused lung tissue develops increased vascular permeability and neutrophil infiltration after reexpansion. This study investigated the lung cellular glutathione system during hypoxia (produced by lung collapse) and after reoxygenation (produced by reexpansion). Two separate groups of rabbits were studied to determine effects of lung hypoxia-reoxygenation on 1) lung glutathione peroxidase and reductase enzyme activities and 2) lung tissue, plasma, and alveolar lavage fluid total (reduced glutathione plus glutathione disulfide) and oxidized glutathione. Neither lung collapse for 3-7 days nor reexpansion for 2 h after 7 days of collapse affected glutathione peroxidase [controls, 0.36 +/- 0.04 (left), 0.38 +/- 0.03 U/mg DNA (right)] or reductase [controls, 0.12 +/- 0.01 (left), 0.14 +/- 0.01 U/mg DNA (right)] activities. The concentration of glutathione disulfide increased markedly in right alveolar lavage fluid, but not in plasma, after right lung reexpansion. Right lung total glutathione decreased significantly (-19%) after 7 days of collapse. After right lung reexpansion, both left (-65%) and right (-68%) lung total glutathione decreased significantly. The percent of total glutathione present in the oxidized form increased significantly in both left (to 15.5 +/- 4.0% of total) and right (to 18.7 +/- 6.3% of total) lungs after reexpansion of the right lung. These data indicate that lung tissue hypoxia, produced by unilateral lung collapse, was associated with a unilateral decrease in lung total glutathione content. Right lung reoxygenation, due to rapid reexpansion, caused a bilateral decrease in lung total glutathione content and an increase in right lung and alveolar lavage fluid glutathione disulfide concentration.


2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Bing Wan ◽  
Yan Li ◽  
Shuangshuang Sun ◽  
Yang Yang ◽  
Yanling LV ◽  
...  

Abstract The present study aimed to investigate the protective effects of ganoderic acid A (GAA) on lipopolysaccharide (LPS)-induced acute lung injury. In mouse model of LPS-induced acute lung injury, we found that GAA led to significantly lower lung wet-to-dry weight ratio and lung myeloperoxidase activity, and attenuated pathological damages. In addition, GAA increased superoxide dismutase activity, but decreased malondialdehyde content and proinflammatory cytokines levels in the bronchoalveolar lavage fluid. Mechanistically, GAA reduced the activation of Rho/ROCK/NF-κB pathway to inhibit LPS-induced inflammation. In conclusion, our study suggests that GAA attenuates acute lung injury in mouse model via the inhibition of Rho/ROCK/NF-κB pathway.


2012 ◽  
Vol 24 (3) ◽  
pp. 588-599 ◽  
Author(s):  
Matthijs G. Bossong ◽  
Gerry Jager ◽  
Hendrika H. van Hell ◽  
Lineke Zuurman ◽  
J. Martijn Jansma ◽  
...  

Deficits in memory function are an incapacitating aspect of various psychiatric and neurological disorders. Animal studies have recently provided strong evidence for involvement of the endocannabinoid (eCB) system in memory function. Neuropsychological studies in humans have shown less convincing evidence but suggest that administration of cannabinoid substances affects encoding rather than recall of information. In this study, we examined the effects of perturbation of the eCB system on memory function during both encoding and recall. We performed a pharmacological MRI study with a placebo-controlled, crossover design, investigating the effects of Δ9-tetrahydrocannabinol (THC) inhalation on associative memory-related brain function in 13 healthy volunteers. Performance and brain activation during associative memory were assessed using a pictorial memory task, consisting of separate encoding and recall conditions. Administration of THC caused reductions in activity during encoding in the right insula, the right inferior frontal gyrus, and the left middle occipital gyrus and a network-wide increase in activity during recall, which was most prominent in bilateral cuneus and precuneus. THC administration did not affect task performance, but while during placebo recall activity significantly explained variance in performance, this effect disappeared after THC. These findings suggest eCB involvement in encoding of pictorial information. Increased precuneus activity could reflect impaired recall function, but the absence of THC effects on task performance suggests a compensatory mechanism. These results further emphasize the eCB system as a potential novel target for treatment of memory disorders and a promising target for development of new therapies to reduce memory deficits in humans.


Perfusion ◽  
2000 ◽  
Vol 15 (5) ◽  
pp. 447-452 ◽  
Author(s):  
Gerard J Myers ◽  
Richard B Leadon ◽  
Lance B Mitchell ◽  
David B Ross

After reviewing all available methods of modified ultrafiltration (MUF), an attempt was made to develop a more simplified approach to this beneficial method of post-bypass fluid removal by withdrawing blood from the right atrium and reinfusing into the aortic cannula (venoarterial). The simplicity of operation, ease of setup and analysis of hemoglobin, hematocrit, total proteins and colloid osmotic pressure, and fluid removed were examined in 12 consecutive neonatal and pediatric patients undergoing cardiac surgery. Results indicate that this simplified modified ultrafiltration (SMUF) is comparable to all other methods of MUF by achieving dramatic improvements in all parameters measured. In addition, SMUF provides the perfusionist with the ability to run conventional ultrafiltration throughout the bypass procedure, using this one circuit design. As well as finding the learning curve for SMUF to be very short, this method was found to be superior in its simplicity of operation, ease of setup, reduced risk of complications and acceptance by the surgeon and anesthetist.


2000 ◽  
Vol 278 (5) ◽  
pp. L914-L922 ◽  
Author(s):  
Toru Arai ◽  
Kin'Ya Abe ◽  
Hiroto Matsuoka ◽  
Mitsuhiro Yoshida ◽  
Masahide Mori ◽  
...  

Interleukin (IL)-10 has been shown to reduce many inflammatory reactions. We investigated the in vivo effects of IL-10 on a bleomycin-induced lung injury model. Hemagglutinating virus of Japan (HVJ)-liposomes containing a human IL-10 expression vector (hIL10-HVJ) or a balanced salt solution as a control (Cont-HVJ) was intraperitoneally injected into mice on day −3. This was followed by intratracheal instillation of bleomycin (0.8 mg/kg) on day 0. Myeloperoxidase activity of bronchoalveolar lavage fluid and tumor necrosis factor-α mRNA expression in bronchoalveolar lavage fluid cells on day 7 and hydroxyproline content of the whole lung on day 21 were inhibited significantly by hIL10-HVJ treatment. However, Cont-HVJ treatment could not suppress any of these parameters. We also examined the in vitro effects of IL-10 on the human lung fibroblast cell line WI-38. IL-10 significantly reduced constitutive and transforming growth factor-β-stimulated type I collagen mRNA expression. However, IL-10 did not affect the proliferation of WI-38 cells induced by platelet-derived growth factor. These data suggested that exogenous IL-10 may be useful in the treatment of pulmonary fibrosis.


2001 ◽  
Vol 85 (5) ◽  
pp. 591-597 ◽  
Author(s):  
S. O. Hoskin ◽  
S. Gavet ◽  
E. Milne ◽  
G. E. Lobley

The present study investigated the relative importance of glutamine as a transamination source in the ovine liver by examination of the labelling of amino acids (AA) in the hepatic free pool, mixed liver and plasma proteins of fed and fasted sheep, following infusion of isotopically-labelled glutamine. In a cross-over design four sheep were either fasted for 3 d or fed to 1·2×energy maintenance and finally euthanased. At each intake, the sheep were infused for 6 h with [2-15N]glutamine (150 μmol/h) and samples of total plasma protein isolated. Following the terminal infusion, liver tissue total proteins were prepared and hydrolysed and15N-enrichments in seventeen AA were determined by GC–combustion–isotope-ratio mass spectrometry. All AA were enriched (relative to natural abundance) except lysine and threonine, with the lowest enrichments in phenylalanine and histidine. There was no effect of the fedv.fasted state, except for leucine and isoleucine in liver protein (P<0·05). Enrichments in liver protein were greater than in plasma protein (P<0·01, except proline) and probably reflect the faster turnover rate of hepatic constitutive proteins compared with export proteins. Amination to methionine was greater than that to phenylalanine (P<0·01), suggesting a mechanism for preferentially protecting the former. This factor could be important for ruminant production, as methionine is often considered to be the first limiting AA for animals offered certain silages and conserved forages. Enrichments in all AA (except for glutamine, alanine and aspartate) were less than that for glutamate (P<0·01), and thus transaminations may have occurred with glutamine directly or via glutamate, following the action of hepatic glutaminase.


1999 ◽  
Vol 277 (2) ◽  
pp. L310-L319 ◽  
Author(s):  
M. Kamochi ◽  
F. Kamochi ◽  
Y. B. Kim ◽  
S. Sawh ◽  
J. M. Sanders ◽  
...  

The role of leukocyte adhesion molecules in endotoxin-induced organ injury was evaluated by administering intraperitoneal Salmonella enteritidislipopolysaccharide (LPS) to wild-type (WT) mice, P-selectin-deficient mice, intercellular adhesion molecule (ICAM)-1-deficient mice, and P-selectin-ICAM-1 double-mutant mice. In WT mice, there was a sevenfold increase in the number of neutrophils present in the pulmonary vascular lavage fluid, and there were sevenfold more intracapillary neutrophils by electron-microscopic (EM) morphometry at 4 h after intraperitoneal LPS compared with that in control mice. Extravascular albumin accumulation increased approximately twofold in the lungs and liver of WT mice treated with LPS. In the double-mutant mice, although overall mortality after intraperitoneal LPS was not attenuated, there was a significant delay in mortality in the P-selectin-ICAM-1-deficient mutants compared with that in WT mice after intraperitoneal LPS ( P < 0.01). Moreover, compared with LPS-treated WT mice, lung and liver extravascular albumin accumulation was significantly lower in LPS-treated P-selectin-ICAM-1 double-mutant mice. Lung myeloperoxidase activity, normalized per 1,000 circulating neutrophils, increased after endotoxin in WT and P-selectin-deficient mice but not in P-selectin-ICAM-1 double-mutant mice. In addition, lung and liver myeloperoxidase activity per 1,000 circulating neutrophils in endotoxin-treated ICAM-1-deficient mice and P-selectin-ICAM-1 double mutants was significantly lower compared with that in endotoxin-treated WT mice. These data suggest that P-selectin and ICAM-1 significantly contribute to lung and liver injury after systemic endotoxemia.


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