Acute bacterial pneumonia in rats increases alveolar epithelial fluid clearance by a tumor necrosis factor-alpha-dependent mechanism.

Rezaiguia, S.; Garat, Chrystelle; Delclaux, Christophe; Meignan, Michel; Fleury, J; Legrand, Patrick; Matthay, Michael A.; Jayr, Christian

doi:10.1172/jci119161

Cited by 160 publications

(131 citation statements)

References 58 publications

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“…fluid clearance, was preserved in a bacteria-induced model of acute lung injury [21] in which decreases in both VEGF mRNA and VEGF protein were shown [5]. The number of alveolar type II epithelial cells was increased, in keeping with previous studies in ARDS demonstrating similar increases in numbers, as well as elevation of epithelial growth factors [1,22,23].…”

Section: Vascular Endothelial Growth Factor and Ards Y Abadie Et Alsupporting

confidence: 86%

Decreased VEGF concentration in lung tissue and vascular injury during ARDS

Abadie

Brégeon²,

Papazian³

et al. 2005

European Respiratory Journal

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Endothelial injury is an important prognostic factor in acute respiratory distress syndrome (ARDS). Decreased production of vascular endothelial growth factor (VEGF) in ARDS may favour vascular lesions, since VEGF promotes endothelial survival by inhibiting apoptosis.This study sought to document low VEGF levels in lung tissue from ARDS patients, to determine whether the cause was injury to alveolar type II cells (the main pulmonary source of VEGF) and to evaluate the vascular consequences. Lung specimens were obtained by open biopsy or autopsy from 29 patients with severe ARDS (two survivors) and five controls.As compared with controls, homogenates of lung tissue from ARDS patients contained less VEGF (median (interquartile range) ARDS 8.2 (4.7-12.2) versus controls 28.4 (9.9-47.1) ng?g -1 protein). Increased immunostaining with surfactant protein B was seen in ARDS lungs. Extensive cellular apoptosis (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling staining), including endothelial and alveolar type II cells, was demonstrated, and vascular bed density (CD31 immunostaining) decreased in ARDS lungs as compared with controls. VEGF levels were negatively correlated to apoptotic endothelial cell counts.In conclusion, decreased vascular endothelial growth factor levels in lung tissue may participate in the decrease in lung perfusion in acute respiratory distress syndrome.

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Section: Vascular Endothelial Growth Factor and Ards Y Abadie Et Alsupporting

confidence: 86%

Decreased VEGF concentration in lung tissue and vascular injury during ARDS

Abadie

Brégeon²,

Papazian³

et al. 2005

European Respiratory Journal

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“…Notably, in the present study, the biphasic modulation of α-ENaC expression, with an increase at 8 h followed by a decrease thereafter, may explain the contradictory reports concerning ENaC expression following endotoxin or bacteria infection in the lung. Instillation of endotoxin into rat lungs and acute bacterial pneumonia in rats has been found to upregulate sodium transport and increase alveolar epithelial fluid clearance (21,22). However, in late pneumonia or severe ALI with pulmonary edema, a significant decrease in α-ENaC expression has been identified, which is associated with a reduced ability for lung fluid clearance (22).…”

Section: Discussionmentioning

confidence: 99%

Biphasic modulation of α-ENaC expression by lipopolysaccharide in vitro and in vivo

Sheng

Nie

et al. 2014

Molecular Medicine Reports

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Abstract. Acute lung injury (ALI) is characterized by pulmonary edema, in which the epithelial sodium channel (ENaC) has a critical role in the clearance of edema fluid from the alveolar space. Lipopolysaccharide (LPS), frequently employed to induce ALI in experimental animal models, has been reported to regulate ENaC expression and alveolar fluid clearance. The role of LPS in regulating ENaC expression is currently controversial, with increases and decreases reported in ENaC expression in response to LPS treatment, as well as reports that ENaC expression is not affected by LPS induction. The present study aimed to systematically analyze the regulation of α-ENaC expression in LPS models of ALI at different pathological stages in vitro and in vivo. ENaC expression was observed to increase ≤8 h after LPS treatment, and to decrease thereafter. This finding may explain the contradictory data regarding α-ENaC expression in response to LPS in the lung. The results of the present study, in combination with those of previous studies, indicate that the modulation of α-ENaC expression may not be a direct genetic response to LPS exposure, but a general response of the lung to the pathological changes associated with inflammation, hypoxia and endothelial and epithelial damage involved in the development of ALI. The findings of this study may have potential clinical significance for understanding the pathogenesis of ALI and improving patient outcome. IntroductionAcute lung injury (ALI) is a clinical syndrome characterized by pulmonary edema and associated with a high mortality rate (1).The pathogenesis of ALI is poorly understood; however, clinical studies have demonstrated that the regulation of epithelial sodium channel (ENaC)-mediated alveolar fluid clearance may represent an effective treatment strategy to improve the outcome for patients with ALI (2,3). ENaC is composed of three homologous subunits, α, β and γ (4). The α subunit is essential for the functional transport of Na + and H 2 O out of the airway lumen. The physiological importance of α-ENaC in the lung has been demonstrated in a study of α-ENaC-knockout mice, where respiratory distress and mortality were observed ≤40 h after birth, as a consequence of an inability to clear fluid from the lungs (5). Furthermore, experimental evidence has indicated that a reduction in α-ENaC expression may impair the resolution of pulmonary edema in patients with ALI (6).To investigate the molecular mechanisms associated with ALI, a variety of experimental models have been used. The induction of lung injury using intra-tracheal administration of lipopolysaccharide (LPS) has represented a useful model for studying ALI, as it avoids multi-organ failure (7). LPS is a prototypical endotoxin that is a key component of the outer membrane of gram-negative bacteria, including Pseudomonas aeruginosa. LPS has been demonstrated to modify Na + transport in the airway epithelium by regulating either ENaC mRNA expression (8) or the ENaC channel current (9). The effect of LPS on α-ENaC express...

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“…2, 9, and 10) are not presently known. However, Rezaiguia et al (52) demonstrated that acute pneumonia with PA in rats increases fluid clearance from the lung, a process that is associated with acute lung injury. Additional studies should determine whether CFTR has a role in the coordination of fluid dynamics and host-pathogen interactions during PA pneumonia.…”

Section: Discussionmentioning

confidence: 99%

Role of Cystic Fibrosis Transmembrane Conductance Regulator in Pulmonary Clearance of Pseudomonas aeruginosa In Vivo

Chroneos

Wert

Livingston

et al. 2000

The Journal of Immunology

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Cystic fibrosis (CF)2 is a fatal genetic disease caused by mutations in the CF transmembrane conductance regulator (CFTR) that is commonly associated with chronic pulmonary infections with mucoid Pseudomonas aeruginosa (PA). To test the hypothesis that CFTR plays a direct role in PA adhesion and clearance, we have used mouse lines expressing varying levels of human (h) or mouse (m) CFTR. A subacute intratracheal dose of 3 × 106 bacteria was cleared with similar kinetics in control wild-type (WT) and transgenic mice overexpressing hCFTR in the lung from the surfactant protein C (SP-C) promoter (SP-C-hCFTR+/−). In a second series of experiments, the clearance of an acute intratracheal dose of 1.5 × 107 PA bacteria was also similar in WT, hemizygous SP-C-hCFTR+/−, and bitransgenic gut-corrected FABP-hCFTR+/+-mCFTR−/−, the latter lacking expression of mCFTR in the lung. However, a small but significant decrease in bacterial killing was observed in lungs of homozygote SP-C-hCFTR+/+ mice. Lung pathology in both WT and SP-C-hCFTR+/+ mice was marked by neutrophilic inflammation and bacterial invasion of perivascular and subepithelial compartments. Bacteria were associated primarily with leukocytes and were not associated with alveolar type II or bronchiolar epithelial cells, the cellular sites of SP-C-hCFTR+/+ transgene expression. The results indicate that there is no direct correlation between levels of CFTR expression and bacterial clearance or association of bacteria with epithelial cells in vivo.

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Acute bacterial pneumonia in rats increases alveolar epithelial fluid clearance by a tumor necrosis factor-alpha-dependent mechanism.

Cited by 160 publications

References 58 publications

Decreased VEGF concentration in lung tissue and vascular injury during ARDS

Decreased VEGF concentration in lung tissue and vascular injury during ARDS

Biphasic modulation of α-ENaC expression by lipopolysaccharide in vitro and in vivo

Role of Cystic Fibrosis Transmembrane Conductance Regulator in Pulmonary Clearance of Pseudomonas aeruginosa In Vivo

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