Lipopolysaccharide induced pulmonary endothelial barrier disruption and lung edema: critical role for bicarbonate and stimulation of AC10.

08:00 EDT 16th October 2015 | BioPortfolio

Summary of "Lipopolysaccharide induced pulmonary endothelial barrier disruption and lung edema: critical role for bicarbonate and stimulation of AC10."

Bacterial induced sepsis is a common cause of pulmonary endothelial barrier dysfunction and can progress toward acute respiratory distress syndrome (ARDS). Elevations in intracellular cAMP tightly regulate pulmonary endothelial barrier integrity; however, cAMP signals are highly compartmentalized and it depends on which compartment the signal is generated - plasma membrane versus cytosolic - as to whether it is barrier protective or disruptive, respectively. The mammalian soluble adenylyl cyclase (AC) isoform 10 (AC10 or sAC) is uniquely stimulated by bicarbonate and is expressed in pulmonary microvascular endothelial cells (PMVECs). Elevated extracellular bicarbonate increases cAMP in PMVECs to disrupt the endothelial barrier and increase the filtration coefficient (Kf) in the isolated lung. Herein, we tested the hypothesis that sepsis-induced endothelial barrier disruption and increased permeability is dependent upon extracellular bicarbonate and activation of AC10. Our findings reveal that LPS-induced endothelial barrier disruption is dependent upon extracellular bicarbonate: LPS-induced barrier failure and increased permeability is exacerbated in elevated bicarbonate compared to low extracellular bicarbonate. The AC10 inhibitor, KH7, attenuated the bicarbonate-dependent LPS-induced barrier disruption. In the isolated lung, LPS failed to increase the Kf in the presence of minimal perfusate bicarbonate. When perfusate bicarbonate was increased to the physiological range (24 mM) this revealed the LPS-induced increase in the Kf, which was attenuated by KH7. Further, when PMVECs were treated with LPS for 6-hours there was a dose-dependent increase in AC10 expression. Thus, these findings reveal that LPS-induced pulmonary endothelial barrier failure requires bicarbonate activation of AC10.


Journal Details

This article was published in the following journal.

Name: American journal of physiology. Lung cellular and molecular physiology
ISSN: 1522-1504
Pages: ajplung.00067.2015


DeepDyve research library

PubMed Articles [18531 Associated PubMed Articles listed on BioPortfolio]

Prolyl hydroxylase domain-2 protein regulates lipopolysaccharide-induced vascular inflammation.

Acute lung injury and its more severe form, the acute respiratory distress syndrome, are life-threatening respiratory disorders. Overwhelming pulmonary inflammation and endothelium disruption are comm...

Endothelial stromelysin1 regulation by the forkhead box-O transcription factors is crucial in the exudative phase of acute lung injury.

Enhanced vascular permeability is associated with inflammation and edema in alveoli during the exudative phase of acute respiratory distress syndrome (ARDS). Mechanisms leading to the endothelial cont...

Role of truncated oxidized phospholipids in acute endothelial barrier dysfunction caused by particulate matter.

Particulate matter (PM) air pollution is a global environmental health problem contributing to more severe lung inflammation and injury. However, the molecular and cellular mechanisms of PM-induced ex...

miR-144 Mediated Inhibition of ROCK1 Protects Against LPS Induced Lung Endothelial Hyperpermeability.

Dysfunctional endothelial cell (EC) barrier and increased lung vascular permeability is a cardinal feature of Acute Lung Injury (ALI) and sepsis that may results in a pathophysiological condition char...

Glucagon-like peptide-1 receptor activation alleviates lipopolysaccharide-induced acute lung injury in mice via maintenance of endothelial barrier function.

Glucagon-like peptide-1 (GLP-1), which is well known for regulating glucose homeostasis, exhibits multiple actions in cardiovascular disorders and renal injury. However, little is known about the effe...

Clinical Trials [12890 Associated Clinical Trials listed on BioPortfolio]

Interaction Diaphragm and Cardiac Function During Ventilator Weaning

Weaning failure is associated with prolonged duration of mechanical ventilation that itself can worsen patient's prognosis. Therefore, identification of the causes and mechanisms leading t...

Performance Evaluation of Clinical Ultrasound in Management of Acute Pulmonary Edema in Elderly Patient

The main objective is to assess the validation of the diagnosis early acute pulmonary edema in elderly patients with acute respiratory distress, admitted in a host of vital emergency servi...

Effect of Acetazolamide on Subclinical High-Altitude Pulmonary Edema Detected by Lung Ultrasonography

The overall goal of this study is to detect preclinical signs of HAPE by lung ultrasonography and evaluate the effectiveness of acetazolamide at decreasing pulmonary edema by using ultraso...

the Effect of Dopamine on Mechanical Ventilation Induced Lung Injury

Dopamine(DA) is a common neurotransmitter that has been known to regulate behavior, movement, cardiovascular,endocrine and gastrointestinal functions, but also functions as an important ...

Neovascularization Induced by Mechanical Barrier disrUption and Systemic Erythropoietin in Patients With Cerebral Perfusion Deficits

Neovascularization Induced by Mechanical Barrier disrUption and Systemic erythropoietin in patients with cerebral perfusion deficits (NIMBUS trial)

Medical and Biotech [MESH] Definitions

Lung damage that is caused by the adverse effects of PULMONARY VENTILATOR usage. The high frequency and tidal volumes produced by a mechanical ventilator can cause alveolar disruption and PULMONARY EDEMA.

A condition of lung damage that is characterized by bilateral pulmonary infiltrates (PULMONARY EDEMA) rich in NEUTROPHILS, and in the absence of clinical HEART FAILURE. This can represent a spectrum of pulmonary lesions, endothelial and epithelial, due to numerous factors (physical, chemical, or biological).

Excessive accumulation of extravascular fluid in the lung, an indication of a serious underlying disease or disorder. Pulmonary edema prevents efficient PULMONARY GAS EXCHANGE in the PULMONARY ALVEOLI, and can be life-threatening.

Absence of air in the entire or part of a lung, such as an incompletely inflated neonate lung or a collapsed adult lung. Pulmonary atelectasis can be caused by airway obstruction, lung compression, fibrotic contraction, or other factors.

Water content outside of the lung vasculature. About 80% of a normal lung is made up of water, including intracellular, interstitial, and blood water. Failure to maintain the normal homeostatic fluid exchange between the vascular space and the interstitium of the lungs can result in PULMONARY EDEMA and flooding of the alveolar space.

Quick Search


DeepDyve research library

Relevant Topics

Pulmonary relating to or associated with the lungs eg Asthma, chronic bronchitis, emphysema, COPD, Cystic Fibrosis, Influenza,  Lung Cancer, Pneumonia, Pulmonary Arterial Hypertension, Sleep Disorders etc Follow and track Lung Cancer News ...

Antiretroviral Therapy Clostridium Difficile Ebola HIV & AIDS Infectious Diseases Influenza Malaria Measles Sepsis Swine Flu Tropical Medicine Tuberculosis Infectious diseases are caused by pathogenic...

Asthma COPD Cystic Fibrosis Pneumonia Pulmonary Medicine Respiratory Respiratory tract infections (RTIs) are any infection of the sinuses, throat, airways or lungs.  They're usually caused by viruses, but they can also ...

Searches Linking to this Article