scholarly journals Sphingomyelin synthase 2 (SMS2) deficiency attenuates LPS-induced lung injury

2011 ◽  
Vol 300 (3) ◽  
pp. L430-L440 ◽  
Author(s):  
Satish Gowda ◽  
Calvin Yeang ◽  
Sunil Wadgaonkar ◽  
Fatima Anjum ◽  
Natalia Grinkina ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Lung Injury ◽  
Pulmonary Edema ◽  
Lung Edema ◽  
Wild Type Littermate ◽  
Littermate Control ◽  
Sphingomyelin Synthase ◽  
Membrane Microdomain ◽  
Permeability Pulmonary Edema

Sphingomyelin synthase (SMS) catalyzes the synthesis of sphingomyelin (SM) and is required for maintenance of plasma membrane microdomain fluidity. Of the two isoforms of mammalian SMS, SMS1 is mostly present in the trans-Golgi apparatus, whereas SMS2 is predominantly found at the plasma membrane. SMS2 has a role in receptor mediated response to inflammation in macrophages, however, the role of SMS2 in vascular permeability, pulmonary edema, and lung injury have not been investigated. To define the role of SMS activation in lung injury, we utilized a lipopolysaccharide (LPS)-induced lung edema model. SMS activity was measured and correlated with the severity of lung injury. Within 4 h of LPS treatment, SMS activity was increased significantly and remained upregulated up to 24 h. Comparison of LPS-induced lung injury in SMS2 knockout (SMS2−/−) and wild-type littermate control mice showed that inflammation, cytokine induction, and lung injury were significantly inhibited in SMS2−/− mice. Our results suggest that a deficiency of SMS2 can diminish the extent of pulmonary edema and lung injury. Furthermore, we show that depletion of SMS2 was sufficient to decrease MAP kinase-JNK activation, severity of LPS-induced pulmonary neutrophil influx, and inflammation, suggesting a novel role of SMS2 activation in lung injury.

scholarly journals Secretory group V phospholipase A2 regulates acute lung injury and neutrophilic inflammation caused by LPS in mice

2009 ◽  
Vol 296 (6) ◽  
pp. L879-L887 ◽  
Author(s):  
Nilda M. Muñoz ◽  
Angelo Y. Meliton ◽  
Lucille N. Meliton ◽  
Steven M. Dudek ◽  
Alan R. Leff
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Lung Edema ◽  
Myeloperoxidase Activity ◽  
Wild Type Littermate ◽  
Littermate Control ◽  
Group V ◽  
Intratracheal Administration ◽  
Neutrophilic Inflammation ◽  
Inducible Protein

We investigated the regulatory role of 14-kDa secretory group V phospholipase A2 (gVPLA2) in the development of acute lung injury (ALI) and neutrophilic inflammation (NI) caused by intratracheal administration of LPS. Experiments were conducted in gVPLA2 knockout ( pla2g5−/−) mice, which lack the gene, and gVPLA2 wild-type littermate control ( pla2g5+/+) mice. Indices of pulmonary injury were evaluated 24 h after intratracheal administration of LPS. Expression of gVPLA2 in microsections of airways and mRNA content in lung homogenates were increased substantially in pla2g5+/+ mice after LPS-administered compared with saline-treated pla2g5+/+ mice. By contrast, expression of gVPLA2 was neither localized in LPS- nor saline-treated pla2g5−/− mice. LPS also caused 1) reduced transthoracic static compliance, 2) lung edema, 3) neutrophilic infiltration, and 4) increased neutrophil myeloperoxidase activity in pla2g5+/+ mice. These events were attenuated in pla2g5−/− mice exposed to LPS or in pla2g5+/+ mice receiving MCL-3G1, a neutralizing MAb directed against gVPLA2, before LPS administration. Our data demonstrate that gVPLA2 is an inducible protein in pla2g5+/+ mice but not in pla2g5−/− mice within 24 h after LPS treatment. Specific inhibition of gVPLA2 with MCL-3G1 or gene-targeted mice lacking gVPLA2 blocks ALI and attenuates NI caused by LPS.

Role of the Splanchnic Nerve and the Adrenal Medulla in the Genesis of ‘Preoptic Pulmonary Edema’

1956 ◽  
Vol 184 (2) ◽  
pp. 351-355 ◽  
Author(s):  
Frederick W. Maire ◽  
Harry D. Patton
Keyword(s):  
Body Weight ◽  
Protective Effect ◽  
Pulmonary Edema ◽  
Adrenal Medulla ◽  
Adrenal Glands ◽  
Splanchnic Nerve ◽  
Lung Edema ◽  
Splanchnic Nerves ◽  
Intact Rats

The pulmonary edema which follows preoptic lesions in rats is prevented by antecedent bilateral section of the splanchnic nerves. Intravenous epinephrine in doses exceeding 0.0125 mg/100 gm body weight causes fatal lung edema in rats comparable to that produced by preoptic lesions. Moreover, extracted pressor amines from rat adrenal glands cause lung edema, often fatal, when injected into the donor or into intact rats. However, adrenal demedullation does not prevent lung edema following preoptic lesions. Hence the protective effect of splanchnectomy against preoptic lesions is not wholly due to adrenal denervation. It is tentatively suggested that preoptic lung edema results from overloading of the pulmonary circuit owing to splanchnic mediated constriction of visceral venous reservoirs. Liver and spleen weights of animals dying from preoptic lung edema were significantly less than normal.

scholarly journals Novel Insights Into Phosgene-Induced Acute Lung Injury in Rats: Role of Dysregulated Cardiopulmonary Reflexes and Nitric Oxide in Lung Edema Pathogenesis

2012 ◽  
Vol 131 (2) ◽  
pp. 612-628 ◽  
Author(s):  
Wenli Li ◽  
Fangfang Liu ◽  
Chen Wang ◽  
Hubert Truebel ◽  
Juergen Pauluhn
Keyword(s):  
Nitric Oxide ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Lung Edema

scholarly journals Angelica Polysaccharide Ameliorates Sepsis-Induced Acute Lung Injury through Inhibiting NLRP3 and NF-κB Signaling Pathways in Mice

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Yan Zhu ◽  
Taocheng Meng ◽  
Aichen Sun ◽  
Jintao Li ◽  
Jinlai Li
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Signaling Pathways ◽  
Cecal Ligation ◽  
Weight Ratio ◽  
Receptor Protein ◽  
Lung Edema ◽  
Caspase 1 ◽  
Tnf Α

Objective. This study aimed to explore the role of angelica polysaccharide (AP) in sepsis-induced acute lung injury (ALI) and its underlying molecular mechanism. Methods. A sepsis model of cecal ligation and puncture (CLP) in male BALB/C mice was used. Then, 24 h after CLP, histopathological changes in lung tissue, lung wet/dry weight ratio, and inflammatory cell infiltration were analyzed. Next, levels of inflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and IL-18), as well as the activity of myeloperoxidase (MPO), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH), were measured to assess the role of AP. The protein expression of NF-κB p65, p-NF-κB p65, IκBα, p-IκBα, nucleotide-binding domain- (NOD-) like receptor protein 3 (NLRP3), ASC, and caspase-1 was detected by western blot. In addition, the expression of p-NF-κB p65 and NLRP3 was detected by immunohistochemistry. Results. AP treatment ameliorated CLP-induced lung injury and lung edema, as well as decreased the number of total cells, neutrophils, and macrophages in bronchoalveolar lavage fluid (BALF). AP reduced the levels of TNF-α, IL-1β, IL-6, and IL-18 in BALF, as well as in serum. Moreover, AP decreased MPO activity and MDA content, whereas increased SOD and GSH levels. AP inhibited the expression of p-NF-κB p65, p-IκBα, NLRP3, ASC, and caspase-1, while promoted IκBα expression. Conclusion. This study demonstrated that AP exhibits protective effects against sepsis-induced ALI by inhibiting NLRP3 and NF-κB signaling pathways in mice.

scholarly journals Levocetirizine Pretreatment Mitigates Lipopolysaccharide-Induced Lung Inflammation in Rats

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Alaa N. A. Fahmi ◽  
George S. G. Shehatou ◽  
Hatem A. Salem
Keyword(s):  
Lung Injury ◽  
Pulmonary Edema ◽  
Lung Tissue ◽  
Weight Ratio ◽  
Tissue Homogenate ◽  
Lung Edema ◽  
Tissue Levels ◽  
Protein Levels ◽  
Lps Challenge ◽  
Ldh Activity

This research was conducted to investigate possible protective influences of levocetirizine, a nonsedatingH1antihistamine, against lipopolysaccharide (LPS)-induced lung injury in rats. Male Sprague Dawley rats received either levocetirizine (1 mg/kg/day, orally) or the vehicle of the drug (2 ml/kg/day, orally) for 1 week before a single IP injection of LPS (7.5 mg/kg). A group of normal rats served as control. The experiments were terminated 18 h after the LPS challenge. Serum C-reactive protein levels were determined. Moreover, total cell count, lactate dehydrogenase (LDH) activity, protein levels, and total NOx were evaluated in bronchoalveolar lavage fluid (BALF). Pulmonary edema was evaluated as the wet/dry lung weight ratio. Lung tissue homogenate was assessed for antioxidant/pro-oxidant status. BALF and lung tissue levels of tumor necrosis factor-α(TNF-α) were assessed. Lungs were examined for histological alterations. LPS-mediated lung injury was manifested by pulmonary edema, leukocyte infiltration, oxidative stress, and inflammation. Levocetirizine attenuated lung edema and mitigated the increases in BALF protein levels, LDH activity, and lung leukocyte recruitment in LPS-challenged rats. Additionally, TNF-αprotein levels in BALF and lung tissue were diminished by levocetirizine administration. Levocetirizine also exhibited a potent antioxidant activity as indicated by a decrease in lung tissue levels of malondialdehyde and an enhancement of superoxide dismutase activity. Histological examination of lung tissues confirmed the beneficial effect of levocetirizine against LPS-induced histopathological alterations. In conclusion, levocetirizine may offer protection against lung tissue damage and inflammation in LPS-challenged rats.

Increased cardiac output increases shunt: role of pulmonary edema and perfusion

1985 ◽  
Vol 59 (4) ◽  
pp. 1313-1321 ◽  
Author(s):  
P. H. Breen ◽  
P. T. Schumacker ◽  
J. Sandoval ◽  
I. Mayers ◽  
L. Oppenheimer ◽  
...  
Keyword(s):  
Cardiac Output ◽  
Oleic Acid ◽  
Pulmonary Edema ◽  
Lung Edema ◽  
Base Line ◽  
Lung Water ◽  
Arteriovenous Fistulas ◽  
Anesthetized Dogs ◽  
The Right

In low-pressure pulmonary edema increased cardiac output (QT) increases shunt (Qs/QT); we tested whether the mechanism is an increase in extravascular lung water in turn mediated by the accompanying increase in microvascular pressure. In six pentobarbital sodium-anesthetized dogs ventilated with O2 we administered oleic acid into the right atrium. From base line to 2 h post-oleic acid we measured concurrent significant increases in Qs/QT (6–29%, O2 technique) and extravascular thermal volume (ETV, 2.6–7.1 ml/g dry intravascular blood-free lung wt, thermal-green dye indicator technique) that were stable by 90 min. Then, bilateral femoral arteriovenous fistulas were opened and closed in 30-min periods to cause reversible increases in QT and associated Qs/QT. When fistulas were open the time-averaged QT increased from 5.1 to 6.9 min (P less than 0.05), the simultaneous Qs/QT rose from 30.7 to 38.4% (P less than 0.05), but ETV did not increase. We conclude that increasing lung edema does not account for our rise in Qs/QT when QT increased.

Recombinant human VEGF treatment transiently increases lung edema but enhances lung structure after neonatal hyperoxia

2006 ◽  
Vol 291 (5) ◽  
pp. L1068-L1078 ◽  
Author(s):  
Anette M. Kunig ◽  
Vivek Balasubramaniam ◽  
Neil E. Markham ◽  
Gregory Seedorf ◽  
Jason Gien ◽  
...  
Keyword(s):  
Lung Injury ◽  
Pulmonary Edema ◽  
Recovery Period ◽  
Weight Ratio ◽  
Lung Edema ◽  
Sprague Dawley ◽  
Lung Weight ◽  
Lung Structure ◽  
Neonatal Hyperoxia ◽  
Enos Protein

Recent studies suggest that VEGF may worsen pulmonary edema during acute lung injury (ALI), but, paradoxically, impaired VEGF signaling contributes to decreased lung growth during recovery from ALI due to neonatal hyperoxia. To examine the diverse roles of VEGF in the pathogenesis of and recovery from hyperoxia-induced ALI, we hypothesized that exogenous recombinant human VEGF (rhVEGF) treatment during early neonatal hyperoxic lung injury may increase pulmonary edema but would improve late lung structure during recovery. Sprague-Dawley rat pups were placed in a hyperoxia chamber (inspired O2 fraction 0.9) for postnatal days 2–14. Pups were randomized to daily intramuscular injections of rhVEGF165 (20 μg/kg) or saline (controls). On postnatal day 14, rats were placed in room air for a 7-day recovery period. At postnatal days 3, 14, and 21, rats were killed for studies, which included body weight and wet-to-dry lung weight ratio, morphometric analysis [including radial alveolar counts (RAC), mean linear intercepts (MLI), and vessel density], and lung endothelial NO synthase (eNOS) protein content by Western blot analysis. Compared with room air controls, hyperoxia increased pulmonary edema by histology and wet-to-dry lung weight ratios at postnatal day 3, which resolved by day 14. Although treatment with rhVEGF did not increase edema in control rats, rhVEGF increased wet-to-dry weight ratios in hyperoxia-exposed rats at postnatal days 3 and 14 ( P < 0.01). Compared with room air controls, hyperoxia decreased RAC and increased MLI at postnatal days 14 and 21. Treatment with VEGF resulted in increased RAC by 181% and decreased MLI by 55% on postnatal day 14 in the hyperoxia group ( P < 0.01). On postnatal day 21, RAC was increased by 176% and MLI was decreased by 58% in the hyperoxia group treated with VEGF. rhVEGF treatment during hyperoxia increased eNOS protein on postnatal day 3 by threefold ( P < 0.05). We conclude that rhVEGF treatment during hyperoxia-induced ALI transiently increases pulmonary edema but improves lung structure during late recovery. We speculate that VEGF has diverse roles in hyperoxia-induced neonatal lung injury, contributing to lung edema during the acute stage of ALI but promoting repair of the lung during recovery.

scholarly journals Role of Caveolin-1 Expression in the Pathogenesis of Pulmonary Edema in Ventilator-Induced Lung Injury

2012 ◽  
Vol 2 (4) ◽  
pp. 452-460 ◽  
Author(s):  
Nikolaos A. Maniatis ◽  
Matina Kardara ◽  
Dan Hecimovich ◽  
Eleftheria Letsiou ◽  
Maricela Castellon ◽  
...  
Keyword(s):  
Lung Injury ◽  
Pulmonary Edema ◽  
Caveolin 1 ◽  
Ventilator Induced Lung Injury

scholarly journals Surfactant Attenuates Air Embolism-Induced Lung Injury by Suppressing NKCC1 Expression and NF-κB Activation

Inflammation ◽  
2020 ◽  
Author(s):  
Chou-Chin Lan ◽  
Yao-Kuang Wu ◽  
Chung-Kan Peng ◽  
Kun-Lun Huang ◽  
Chin-Pyng Wu
Keyword(s):  
Lung Injury ◽  
Pulmonary Edema ◽  
Inflammatory Cytokines ◽  
Lung Inflammation ◽  
Inflammatory Responses ◽  
Air Embolism ◽  
Lower Surface ◽  
Beneficial Effects ◽  
Pro Inflammatory Cytokines

Abstract Excessive amounts of air can enter the lungs and cause air embolism (AE)-induced acute lung injury (ALI). Pulmonary AE can occur during diving, aviation, and iatrogenic invasive procedures. AE-induced lung injury presents with severe hypoxia, pulmonary hypertension, microvascular hyper-permeability, and severe inflammatory responses. Pulmonary AE-induced ALI is a serious complication resulting in significant morbidity and mortality. Surfactant is abundant in the lungs and its function is to lower surface tension. Earlier studies have explored the beneficial effects of surfactant in ALI; however, none have investigated the role of surfactant in pulmonary AE-induced ALI. Therefore, we conducted this study to determine the effects of surfactant in pulmonary AE-induced ALI. Isolated-perfused rat lungs were used as a model of pulmonary AE. The animals were divided into four groups (n = 6 per group): sham, air embolism (AE), AE + surfactant (0.5 mg/kg), and AE+ surfactant (1 mg/kg). Surfactant pretreatment was administered before the induction of pulmonary AE. Pulmonary AE was induced by the infusion of 0.7 cc air through a pulmonary artery catheter. After induction of air, pulmonary AE was presented with pulmonary edema, pulmonary microvascular hyper-permeability, and lung inflammation with neutrophilic sequestration. Activation of NF-κB was observed, along with increased expression of pro-inflammatory cytokines, and Na-K-Cl cotransporter isoform 1 (NKCC1). Surfactant suppressed the activation of NF-κB and decreased the expression of pro-inflammatory cytokines and NKCC1, thereby attenuating AE-induced lung injury. Therefore, AE-induced ALI presented with pulmonary edema, microvascular hyper-permeability, and lung inflammation. Surfactant suppressed the expressions of NF-κB, pro-inflammatory cytokines, and NKCC1, thereby attenuating AE-induced lung injury.

Continuous enteral nutrition attenuates pulmonary edema in rats exposed to 100% oxygen

2000 ◽  
Vol 89 (5) ◽  
pp. 1759-1765 ◽  
Author(s):  
Phillip Factor ◽  
Karen Ridge ◽  
John Alverdy ◽  
Jacob I. Sznajder
Keyword(s):  
Lung Injury ◽  
Pulmonary Edema ◽  
Dry Weight ◽  
Lung Edema ◽  
Sprague Dawley ◽  
Adult Rats ◽  
Sprague Dawley Rats ◽  
Lung Liquid ◽  
And Function ◽  
Protective Proteins

Adult rats exposed to hyperoxia develop anorexia, weight loss, and a lung injury characterized by pulmonary edema and decreased lung liquid clearance. We hypothesized that maintenance of nutrition during hyperoxia could attenuate hyperoxia-induced pulmonary edema. To test this hypothesis, we enterally fed adult male Sprague-Dawley rats via gastrostomy tubes and exposed them to oxygen (inspired O2 fraction >0.95) for 64 h. In contrast to controls, enterally fed hyperoxic animals did not lose weight and had smaller pleural effusions and wet-to-dry weight ratios (a measure of lung edema) that were not different from room air controls. Enterally fed rats exposed to hyperoxia had increased levels of mRNA for the Na+-K+-ATPase α1- and β1-subunits and glutathione peroxidase. These findings suggest that maintenance of nutrition during an oxidative lung injury reduces lung edema, perhaps by allowing for continued expression and function of protective proteins such as the Na+-K+-ATPase.

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