A5045292558- Ion Transport and Channel Regulation
- Neonatal Respiratory Health Research
- Ion channel regulation and function
- Respiratory Support and Mechanisms
- Neuroscience of respiration and sleep
- Transplantation: Methods and Outcomes
- Pancreatic function and diabetes
- Long-Term Effects of COVID-19
- Influenza Virus Research Studies
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Nitric Oxide and Endothelin Effects
- Intensive Care Unit Cognitive Disorders
- Respiratory viral infections research
- Adipose Tissue and Metabolism
- Renal function and acid-base balance
- Immune Response and Inflammation
- Muscle Physiology and Disorders
- Cardiac Arrest and Resuscitation
- Immune cells in cancer
- Organ Transplantation Techniques and Outcomes
- Cancer, Hypoxia, and Metabolism
- Pneumonia and Respiratory Infections
- Renal Transplantation Outcomes and Treatments
- MicroRNA in disease regulation
- Receptor Mechanisms and Signaling
Northwestern University
2015-2024
Northwestern Medicine
2024
Northwestern University
2021-2024
Thoracic Surgery Foundation
2020-2022
Pulmonary and Critical Care Associates
2006-2020
Midwestern University
2006-2017
Pulmonary Associates
2007-2012
Utrecht University
2006
Technion – Israel Institute of Technology
2004-2006
University Medical Center Utrecht
2006
Hypercapnia (elevated CO2 levels) occurs as a consequence of poor alveolar ventilation and impairs fluid reabsorption (AFR) by promoting Na,K-ATPase endocytosis. We studied the mechanisms regulating CO2-induced endocytosis in epithelial cells (AECs) dysfunction rats. Elevated levels caused rapid activation AMP-activated protein kinase (AMPK) AECs, key regulator metabolic homeostasis. Activation AMPK was mediated CO2-triggered increase intracellular Ca2+ concentration...
Elevated CO(2) concentrations (hypercapnia) occur in patients with severe lung diseases. Here, we provide evidence that high levels decrease O(2) consumption and ATP production impair cell proliferation independently of acidosis hypoxia fibroblasts (N12) alveolar epithelial cells (A549). Cells exposed to elevated died galactose medium as well when glucose-6-phosphate isomerase was knocked down, suggesting mitochondrial dysfunction. High led increased microRNA-183 (miR-183), which turn...
Influenza A viruses (IAV) can cause lung injury and acute respiratory distress syndrome (ARDS), which is characterized by accumulation of excessive fluid (edema) in the alveolar airspaces leads to hypoxemia death if not corrected. Clearance excess edema driven mostly epithelial Na,K-ATPase crucial for survival patients with ARDS. We therefore investigated whether IAV infection alters expression function cells (AECs) ability clear edema. reduced plasma membrane human murine AECs distal...
Ischemia reperfusion injury represents a common pathological condition that is triggered by the release of endogenous ligands. While neutrophils are known to play critical role in its pathogenesis, tissue-specific spatiotemporal regulation ischemia-reperfusion not understood. Here, using oxidative lipidomics and intravital imaging transplanted mouse lungs subjected severe ischemia injury, we discovered necroptosis, nonapoptotic form cell death, triggers recruitment neutrophils. During...
In patients with acute respiratory failure, gas exchange is impaired due to the accumulation of fluid in lung airspaces. This life-threatening syndrome treated mechanical ventilation, which adjusted maintain exchange, but can be associated carbon dioxide lung. Carbon (CO2) a by-product cellular energy utilization and its elimination affected via alveolar epithelial cells. Signaling pathways sensitive changes CO2 levels were described plants neuronal mammalian However, it has not been fully...
We set out to determine whether cellular hypoxia, via mitochondrial reactive oxygen species, promotes Na,K-ATPase degradation the ubiquitin-conjugating system. Cells exposed 1.5% O 2 had a decrease in activity and consumption. The total cell pool of α1 protein decreased on exposure for 30 hours, whereas plasma membrane was 50% degraded after hours which prevented by lysosome proteasome inhibitors. When Chinese hamster ovary cells that exhibit temperature-sensitive defect E1 ubiquitin...
Primary graft dysfunction (PGD) is the predominant cause of early loss following lung transplantation. We recently demonstrated that donor pulmonary intravascular nonclassical monocytes (NCM) initiate neutrophil recruitment. Simultaneously, host-origin classical (CM) permeabilize vascular endothelium to allow extravasation necessary for PGD. Here, we show a CCL2-CCR2 axis CM Surprisingly, although intravital imaging and multichannel flow cytometry revealed depletion NCM abrogated...
Ventilator-associated lung injury (VALI) is caused by high tidal volume (Vt) excursions producing microvascular leakage and pulmonary edema. However, the effects of VALI on edema clearance alveolar epithelial cells' Na,K-ATPase function have not been elucidated. We studied in isolated–perfused rat model after ventilation for 25, 40, 60 min with Vt (peak airway opening pressure [Pao] approximately 35 cm H2O) compared them low (Pao ∼ 8 H2O), moderate 20 nonventilated rats. Lung control rats...
Mechanical ventilation with high tidal volume (HVT) causes lung injury and decreases the lung's ability to clear edema in rats. beta-adrenergic agonists increase active Na(+) transport clearance normal rat lungs by stimulating apical channels basolateral Na,K-ATPase alveolar epithelial cells. We studied whether could restore rats ventilated HVT (40 ml/kg, peak airway pressure of 35 cm H(2)O) for 40 min. The decreased approximately 50% after min ventilation. Terbutaline (TERB) isoproterenol...
The purpose of this study was to define mechanisms by which dopamine (DA) regulates the Na,K-ATPase in alveolar epithelial type 2 (AT2) cells. activity increased twofold cells incubated with either 1 μM DA or a dopaminergic D agonist, fenoldopam, but not agonist quinpirole. increase paralleled an α1 and β1 protein abundance basolateral membrane (BLM) AT2 This mediated exocytosis Na,K-pumps from late endosomal compartments into BLM. Down-regulation diacylglycerol-sensitive types kinase C...
β-Adrenergic agonists have been reported to increase lung liquid clearance by stimulating active Na + transport across the alveolar epithelium. We studied mechanisms which β-adrenergic isoproterenol (Iso) increases in isolated perfused fluid-filled rat lungs. Iso through pulmonary circulation at concentrations of 10 −4 −8 M increased compared with that control lungs ( P < 0.01). The was inhibited β-antagonist propranolol (10 −5 M), -channel blocker amiloride and antagonist Na-K-ATPase,...
Exposure of adult rats to 100% O 2 results in lung injury and decreases active sodium transport edema clearance. It has been reported that β-adrenergic agonists increase clearance normal rat lungs by upregulating alveolar epithelial Na + -K -ATPase function. This study was designed examine whether isoproterenol (Iso) affects exposed for 64 h. Active decreased ∼44% acute hyperoxia. Iso (10 −6 M) increased the ability clear room-air-breathing (from 0.50 ± 0.02 0.99 0.05 ml/h) 0.28 0.03 0.86...
Abstract Muscle dysfunction is common in patients with adult respiratory distress syndrome and associated morbidity that can persist for years after discharge. In a mouse model of severe influenza A pneumonia, we found the proinflammatory cytokine IL-6 was necessary development muscle dysfunction. Treatment Food Drug Administration–approved Ab antagonist to IL-6R (tocilizumab) attenuated severity A–induced cultured myotubes, promoted degradation via JAK/STAT, FOXO3a, atrogin-1 upregulation....
The elevation of carbon dioxide (CO2) in tissues and the bloodstream (hypercapnia) occurs patients with severe lung diseases, including chronic obstructive pulmonary disease (COPD). Whereas hypercapnia has been recognized as a marker COPD severity, role for pathogenesis remains unclear. We provide evidence that CO2 acts signaling molecule mouse human airway smooth muscle cells. High activated calcium-calpain consequent cell contraction was mediated by caspase-7-induced down-regulation...
Primary graft dysfunction (PGD) is the leading cause of postoperative mortality in lung transplant recipients and most important risk factor for development chronic allograft dysfunction. The mechanistic basis variability incidence severity PGD between not known. Using a murine orthotopic vascularized model, we found that redundant activation Toll-like receptors 2 4 (TLR2 -4) on nonclassical monocytes activates MyD88, inducing release neutrophil attractant chemokine CXCL2. Deletion Itgam...
Exposure to hyperoxia causes lung injury, decreases active sodium transport and edema clearance in rats. Dopamine (DA) increases by stimulating vectorial Na+ flux Na,K-ATPase function rat alveolar epithelium. This study was designed test whether DA (10− 5 M) would increase rats exposed 100% O2 for 64 h. Active decreased approximately 44% acute (p < 0.001). increased room air breathing (from 0.50 ± 0.02 0.75 0.06 ml/h) 0.28 0.03 0.67 ml/h). Disruption of cell microtubular system colchicine...
Mechanical ventilation is a valuable treatment regimen for respiratory failure. However, mechanical (especially with high tidal volumes) implicated in the initiation and/or exacerbation of lung injury. Hence, it important to understand how cells that line inner surface [alveolar epithelial (AECs)] sense cyclic stretching. Here, we tested hypothesis matrix molecules, via their interaction receptors, transduce signals AECs. We first determined rat AECs secrete an extracellular (ECM) rich...
Hypoxia impairs alveolar fluid reabsorption by promoting Na,K-ATPase endocytosis, from the plasma membrane of epithelial cells. The present study was designed to determine whether hypoxia induces endocytosis via reactive oxygen species (ROS)-mediated RhoA activation. In A549 cells, activation occurred within 15 minutes cells exposure hypoxia. This inhibited in infected with adenovirus coding for gluthatione peroxidase (an H2O2 scavenger), mitochondria depleted (rho0) or expressing decreased...