5 results on '"Raja-Elie E. Abdulnour"'
Search Results
2. Cysteinyl maresins regulate the prophlogistic lung actions of cysteinyl leukotrienes
- Author
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Bruce D. Levy, Yan Bai, Charles N. Serhan, Raja-Elie E. Abdulnour, Xingbin Ai, Paul C. Norris, Thayse Regina Brüggemann, and Alexander H. Tavares
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0301 basic medicine ,Leukotrienes ,Docosahexaenoic Acids ,Immunology ,Inflammation ,Article ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Animals ,Humans ,Immunology and Allergy ,Medicine ,Maresin ,Cysteine ,Lung ,House dust mite ,Leukotriene ,medicine.diagnostic_test ,biology ,business.industry ,respiratory system ,biology.organism_classification ,Asthma ,respiratory tract diseases ,Cysteinyl leukotriene receptor 1 ,Ovalbumin ,030104 developmental biology ,Bronchoalveolar lavage ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Lipidomics ,biology.protein ,Leukotriene Antagonists ,medicine.symptom ,business - Abstract
Background Cysteinyl leukotrienes (CysLTs) are potent prophlogistic mediators in asthmatic patients; however, inhibition of CysLT receptor 1 is not a consistently effective treatment, suggesting additional regulatory mechanisms. Other cysteinyl-containing lipid mediators (LMs) derived from docosahexaenoic acid, namely maresin conjugates in tissue regeneration (MCTRs), were recently discovered. Therefore their production and actions in the lung are of considerable interest. Objective We sought to determine MCTR production, bioactions, and mechanisms in the human lung and in patients with experimental allergic airway inflammation. Methods LM metabololipidomic profiling of the lung was performed by using liquid chromatography with tandem mass spectrometry. Donor-derived human precision-cut lung slices were exposed to leukotriene (LT) D4, MCTRs, or both before determination of airway contraction. The actions of exogenous MCTRs on murine allergic host responses were determined in the setting of ovalbumin- and house dust mite–induced lung inflammation. Results Lipidomic profiling showed that the most abundant cysteinyl LMs in healthy human lungs were MCTRs, whereas CysLTs were most prevalent in patients with disease. MCTRs blocked LTD4-initiated airway contraction in human precision-cut lung slices. In mouse allergic lung inflammation MCTRs were present with temporally regulated production. With ovalbumin-induced inflammation, MCTR1 was most potent for promoting resolution of eosinophils, and MCTR3 potently decreased airway hyperreactivity to methacholine, bronchoalveolar lavage fluid albumin, and serum IgE levels. MCTR1 and MCTR3 inhibited lung eosinophilia after house dust mite–induced inflammation. Conclusion These results identified lung MCTRs that blocked human LTD4-induced airway contraction and promoted resolution of murine allergic airway responses when added exogenously. Together, these findings uncover proresolving mechanisms for lung responses that can be disrupted in patients with disease.
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- 2020
3. Resolvin D3 and Aspirin-Triggered Resolvin D3 Are Protective for Injured Epithelia
- Author
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Souheil El-Chemaly, Jesmond Dalli, Jennifer K. Colby, Nicos A. Petasis, Romain A. Colas, Jason Hellmann, Bruce D. Levy, Charles N. Serhan, Matthew Spite, Ye Cui, Raja-Elie E. Abdulnour, Jeremy W. Winkler, Blenda Wong, and Ho Pan Sham
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Male ,0301 basic medicine ,Epithelial sodium channel ,medicine.medical_specialty ,Acute Lung Injury ,Blotting, Western ,Inflammation ,Biology ,Lung injury ,Pathology and Forensic Medicine ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Edema ,Internal medicine ,medicine ,Animals ,Mice, Inbred BALB C ,Aspirin ,medicine.diagnostic_test ,Regular Article ,Immunohistochemistry ,3. Good health ,Disease Models, Animal ,030104 developmental biology ,Endocrinology ,Bronchoalveolar lavage ,chemistry ,Docosahexaenoic acid ,Immunology ,Fatty Acids, Unsaturated ,Keratinocyte growth factor ,medicine.symptom ,Resolvin ,030215 immunology - Abstract
Acute lung injury is a life-threatening condition caused by disruption of the alveolar-capillary barrier leading to edema, influx of inflammatory leukocytes, and impaired gas exchange. Specialized proresolving mediators biosynthesized from essential fatty acids, such as docosahexaenoic acid, have tissue protective effects in acute inflammation. Herein, we found that the docosahexaenoic acid–derived mediator resolvin D3 (RvD3): 4 S ,11 R ,17 S -trihydroxydocosa-5 Z ,7 E ,9 E ,13 Z ,15 E ,19 Z -hexaenoic acid was present in uninjured lungs, and increased significantly 24 to 72 hours after hydrochloric acid–initiated injury. Because of its delayed enzymatic degradation, we used aspirin-triggered (AT)-RvD3: 4 S ,11 R ,17 R -trihydroxydocosa-5 Z ,7 E ,9 E ,13 Z ,15 E ,19 Z -hexaenoic acid, a 17 R -epimer of RvD3, for in vivo experiments. Histopathological correlates of acid injury (alveolar wall thickening, edema, and leukocyte infiltration) were reduced in mice receiving AT-RvD3 1 hour after injury. AT-RvD3–treated mice had significantly reduced edema, as demonstrated by lower wet/dry weight ratios, increased epithelial sodium channel γ expression, and more lymphatic vessel endothelial hyaluronan receptor 1-positive vascular endothelial growth factor receptor 3-positive lymphatic vessels. Evidence for counterregulation of NF-κB by RvD3 and AT-RvD3 was seen in vitro and by AT-RvD3 in vivo . Increases in lung epithelial cell proliferation and bronchoalveolar lavage fluid levels of keratinocyte growth factor were observed with AT-RvD3, which also promoted cutaneous re-epithelialization. Together, these data demonstrate protective actions of RvD3 and AT-RvD3 for injured mucosa that accelerated restoration of epithelial barrier and function.
- Published
- 2016
4. Silencing Nociceptor Neurons Reduces Allergic Airway Inflammation
- Author
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Maud Pascal, Josef M. Penninger, Simmie L. Foster, Raja-Elie E. Abdulnour, Isaac M. Chiu, Vijay K. Kuchroo, David Roberson, Bruce P. Bean, Clifford J. Woolf, Oliver Haworth, Christian A. von Hehn, Shane J. F. Cronin, Sébastien Talbot, Matthew DiBiase, Busranour Agac, Cédric J. Laedermann, Bruce D. Levy, Patrick R. Burkett, Seungkyu Lee, Johnathan V. Tran, Hiroyuki Seki, Nicole Y. Lai, and Nader Ghasemlou
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biology ,Chemistry ,General Neuroscience ,medicine.medical_treatment ,Sodium channel ,Neuroscience(all) ,Vasoactive intestinal peptide ,Article ,respiratory tract diseases ,3. Good health ,Allergic inflammation ,Ovalbumin ,Cytokine ,Immune system ,nervous system ,Immunology ,medicine ,Nociceptor ,biology.protein ,Gene silencing - Abstract
SummaryLung nociceptors initiate cough and bronchoconstriction. To elucidate if these fibers also contribute to allergic airway inflammation, we stimulated lung nociceptors with capsaicin and observed increased neuropeptide release and immune cell infiltration. In contrast, ablating Nav1.8+ sensory neurons or silencing them with QX-314, a charged sodium channel inhibitor that enters via large-pore ion channels to specifically block nociceptors, substantially reduced ovalbumin- or house-dust-mite-induced airway inflammation and bronchial hyperresponsiveness. We also discovered that IL-5, a cytokine produced by activated immune cells, acts directly on nociceptors to induce the release of vasoactive intestinal peptide (VIP). VIP then stimulates CD4+ and resident innate lymphoid type 2 cells, creating an inflammatory signaling loop that promotes allergic inflammation. Our results indicate that nociceptors amplify pathological adaptive immune responses and that silencing these neurons with QX-314 interrupts this neuro-immune interplay, revealing a potential new therapeutic strategy for asthma.
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- 2015
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5. Negative Pressure Pulmonary Edema Following Bronchospasm
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Raja-Elie E. Abdulnour, Edward A. Bittner, David J. Krodel, Robert H. Brown, and Matthias Eikermann
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Adult ,Pulmonary and Respiratory Medicine ,medicine.medical_treatment ,Pulmonary Edema ,Critical Care and Intensive Care Medicine ,Bronchospasm ,Diagnosis, Differential ,Positive-Pressure Respiration ,Electrocardiography ,Bronchial Spasm ,Intubation, Intratracheal ,medicine ,Humans ,Intubation ,Reactive airway disease ,medicine.diagnostic_test ,business.industry ,respiratory system ,Pulmonary edema ,medicine.disease ,Respiratory Function Tests ,respiratory tract diseases ,Echocardiography ,Anesthesia ,Heart failure ,Anesthetic ,Female ,medicine.symptom ,Tomography, X-Ray Computed ,Cardiology and Cardiovascular Medicine ,business ,medicine.drug - Abstract
Negative pressure pulmonary edema (NPPE) is an important cause of noncardiogenic pulmonary edema but is rarely reported in the setting of bronchospasm. A 43-year-old woman with severe reactive airway disease suffered an episode of severe bronchospasm after endotracheal extubation following an otherwise uneventful general anesthetic. Subsequently, she developed clinical and radiographic signs of pulmonary edema in the absence of other symptoms of acute left-sided heart failure, leading to the diagnosis of noncardiogenic pulmonary edema. She received noninvasive positive pressure ventilation for a few hours, after which her clinical and radiologic signs and symptoms of pulmonary edema were greatly improved. This clinical scenario strongly suggests NPPE. We submit that it is possible to create NPPE by generating highly negative intrathoracic pressures in the setting of severe bronchospasm.
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- 2011
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