scholarly journals A genetic variant of cortactin linked to acute lung injury impairs lamellipodia dynamics and endothelial wound healing

2015 ◽  
Vol 309 (9) ◽  
pp. L983-L994 ◽  
Author(s):  
Sangwook Choi ◽  
Sara M. Camp ◽  
Arkaprava Dan ◽  
Joe G. N. Garcia ◽  
Steven M. Dudek ◽  
...  
Keyword(s):  
Wound Healing ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Regulatory Protein ◽  
Actin Binding ◽  
Gap Closure ◽  
Sphingosine 1 Phosphate ◽  
Endothelial Wound Healing ◽  
Genetic Signatures ◽  
The Impact

Inflammatory mediators released in acute lung injury (ALI) trigger the disruption of interendothelial junctions, leading to loss of vascular barrier function, protein-rich pulmonary edema, and severe hypoxemia. Genetic signatures that predict patient recovery or disease progression are poorly defined, but recent genetic screening of ALI patients has identified an association between lung inflammatory disease and a single nucleotide polymorphism (SNP) in the gene for the actin-binding and barrier-regulatory protein cortactin. This study investigated the impact of this disease-linked cortactin variant on wound healing processes that may contribute to endothelial barrier restoration. A microfabricated platform was used to quantify wound healing in terms of gap closure speed, lamellipodia dynamics, and cell velocity. Overexpression of wild-type cortactin in endothelial cells (ECs) improved directional cell motility and enhanced lamellipodial protrusion length, resulting in enhanced gap closure rates. By contrast, the cortactin SNP impaired wound closure and cell locomotion, consistent with the observed reduction in lamellipodial protrusion length and persistence. Overexpression of the cortactin SNP in lung ECs mitigated the barrier-enhancing activity of sphingosine 1-phosphate. These findings suggest that this common cortactin variant may functionally contribute to ALI predisposition by impeding endothelial wound healing.

Apolipoprotein M Protects Against Lipopolysaccharide-Induced Acute Lung Injury via Sphingosine-1-Phosphate Signaling

Inflammation ◽  
2017 ◽  
Vol 41 (2) ◽  
pp. 643-653 ◽  
Author(s):  
Bin Zhu ◽  
Guang-hua Luo ◽  
Yue-hua Feng ◽  
Miao-mei Yu ◽  
Jun Zhang ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Apolipoprotein M ◽  
Sphingosine 1 Phosphate

scholarly journals Emodin alleviates LPS-induced inflammatory response in lung injury rat by affecting the function of neutrophils

2020 ◽  
Author(s):  
Hongxia Mei ◽  
Ying Tao ◽  
Tianhao Zhang ◽  
Feng Qi
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Response ◽  
Rat Model ◽  
Neutrophil Function ◽  
Life Threatening ◽  
Pulmonary Inflammatory Response ◽  
Anti Inflammatory ◽  
Factor Α ◽  
The Impact

Abstract Background: Acute lung injury (ALI) and/or acute respiratory distress syndrome (ARDS) are critical life-threatening syndromes characterized by the infiltration of a large number of neutrophils that lead to an excessive inflammatory response. Emodin (Emo) is a naturally occurring anthraquinone derivative and an active ingredient of Chinese medicine. It is believed to have anti-inflammatory effects. In this study, we examined the impact of Emo on the pulmonary inflammatory response and the neutrophil function in a rat model of lipopolysaccharide (LPS)-induced ALI.Results: Treatment with Emo protected rat against LPS-induced ALI. Compared to untreated rat, Emo-treated rat exhibited significantly ameliorated lung pathological changes and decreased tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). However, Emo has no protective effect on the rat model of acute lung injury with neutrophil deficiency. In addition, treatment with Emo enhanced the bactericidal capacity of LPS-induced neutrophils via the up-regulation of the ability of neutrophils to phagocytize bacteria and generate neutrophil extracellular traps (NETs). Emo also downregulated the neutrophil respiratory burst and the expression of reactive oxygen species (ROS) in LPS-stimulated neutrophils, alleviating the damage of neutrophils to surrounding tissues. Finally, Emo can accelerate the resolution of inflammation by promoting apoptosis of neutrophils. Conclusion: Our results provide the evidence that Emo could ameliorates LPS-induced ALI via its anti-inflammatory action by modulating the function of neutrophils. Emo may be a promising preventive and therapeutic agent in the treatment of ALI.

scholarly journals Sphingosine-1–Phosphate, FTY720, and Sphingosine-1–Phosphate Receptors in the Pathobiology of Acute Lung Injury

2013 ◽  
Vol 49 (1) ◽  
pp. 6-17 ◽  
Author(s):  
Viswanathan Natarajan ◽  
Steven M. Dudek ◽  
Jeffrey R. Jacobson ◽  
Liliana Moreno-Vinasco ◽  
Long Shuang Huang ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Sphingosine 1 Phosphate

Effect of Thoracentesis on Intubated Patients with Acute Lung Injury

2016 ◽  
Vol 82 (3) ◽  
pp. 266-270
Author(s):  
Matthew B. Bloom ◽  
Derek Serna-Gallegos ◽  
Mark Ault ◽  
Ahsan Khan ◽  
Rex Chung ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Blood Gases ◽  
Surgical Intensive Care Unit ◽  
Surgical Intensive Care ◽  
Mechanically Ventilated ◽  
Arterial Blood ◽  
Tertiary Center ◽  
Before And After ◽  
The Impact

Pleural effusions occur frequently in mechanically ventilated patients, but no consensus exists regarding the clinical benefit of effusion drainage. We sought to determine the impact of thoracentesis on gas exchange in patients with differing severities of acute lung injury (ALI). A retrospective analysis was conducted on therapeutic thoracenteses performed on intubated patients in an adult surgical intensive care unit of a tertiary center. Effusions judged by ultrasound to be 400 mL or larger were drained. Subjects were divided into groups based on their initial P:F ratios: normal >300, ALI 200 to 300, and acute respiratory distress syndrome (ARDS) <200. Baseline characteristics, physiologic variables, arterial blood gases, and ventilator settings before and after the intervention were analyzed. The primary end point was the change in measures of oxygenation. Significant improvements in P:F ratios (mean ± SD) were seen only in patients with ARDS (50.4 ± 38.5, P = 0.001) and ALI (90.6 ± 161.7, P = 0.022). Statistically significant improvement was observed in the pO2 (31.1, P = 0.005) and O2 saturation (4.1, P < 0.001) of the ARDS group. The volume of effusion removed did not correlate with changes in individual patient's oxygenation. These data support the role of therapeutic thoracentesis for intubated patients with abnormal P:F ratios.

The impact of pretreatment with bolus dose of enteral glutamine on acute lung injury induced by oleic acid in rats

2013 ◽  
Vol 28 (3) ◽  
pp. 354-362 ◽  
Author(s):  
A. Ebru Salman ◽  
Fahri Yetişir ◽  
Mehmet Kılıç ◽  
Özkan Önal ◽  
Ahmet Dostbil ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Oleic Acid ◽  
Lung Injury ◽  
Bolus Dose ◽  
The Impact

scholarly journals Recent advances in genetic predisposition to clinical acute lung injury

2009 ◽  
Vol 296 (5) ◽  
pp. L713-L725 ◽  
Author(s):  
Li Gao ◽  
Kathleen C. Barnes
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Candidate Genes ◽  
Genetic Variants ◽  
Complex Traits ◽  
Association Studies ◽  
Genetic Association Studies ◽  
Special Focus ◽  
Disease Manifestation ◽  
The Impact

It has been well established that acute lung injury (ALI), and the more severe presentation of acute respiratory distress syndrome (ARDS), constitute complex traits characterized by a multigenic and multifactorial etiology. Identification and validation of genetic variants contributing to disease susceptibility and severity has been hampered by the profound heterogeneity of the clinical phenotype and the role of environmental factors, which includes treatment, on outcome. The critical nature of ALI and ARDS, compounded by the impact of phenotypic heterogeneity, has rendered the amassing of sufficiently powered studies especially challenging. Nevertheless, progress has been made in the identification of genetic variants in select candidate genes, which has enhanced our understanding of the specific pathways involved in disease manifestation. Identification of novel candidate genes for which genetic association studies have confirmed a role in disease has been greatly aided by the powerful tool of high-throughput expression profiling. This article will review these studies to date, summarizing candidate genes associated with ALI and ARDS, acknowledging those that have been replicated in independent populations, with a special focus on the specific pathways for which candidate genes identified so far can be clustered.

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