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Brief Glutamine Pretreatment Increases Alveolar Macrophage CD163/Heme Oxygenase-1/p38-MAPK Dephosphorylation Pathway and Decreases Capillary Damage but Not Neutrophil Recruitment in IL-1/LPS-Insufflated Rats.

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Date
2015
Authors
Fernandez-Bustamante, Ana
Agazio, Amanda
Wilson, Paul
Elkins, Nancy
Domaleski, Luke
He, Qianbin
Baer, Kaily A
Moss, Angela FD
Wischmeyer, Paul E
Repine, John E
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Abstract
BACKGROUND: Glutamine (GLN) attenuates acute lung injury (ALI) but its effect on alveolar macrophages is unknown. We hypothesized that GLN pretreatment would induce the anti-inflammatory CD163/heme oxygenase (HO)-1/p38-MAPK dephosphorylation pathway in alveolar macrophages and reduce ALI in rats insufflated with interleukin-1 (IL-1) and lipopolysaccharide (LPS). METHODS: Male Sprague-Dawley rats were randomized to the following groups: GLN-IL-1/LPS-, GLN+IL-1/LPS-, GLN-IL-1/LPS+, and GLN+IL-1/LPS+. GLN pretreatment was given via gavage (1 g/kg L-alanyl-L-glutamine) daily for 2 days. ALI was subsequently induced by insufflating 50 ng IL-1 followed by 5mg/kg E.coli LPS. After 24h, bronchoalveolar lavage (BAL) protein, lactate dehydrogenase (LDH) and neutrophil concentrations were analyzed. BAL alveolar macrophage CD163+ expression, HO-1 and p38-MAPK concentrations were measured, as well as alveolar macrophage tumor necrosis factor (TNF)-α and interleukin (IL)-10 concentrations. Histology and immunofluorescence studies were also performed. RESULTS: Following IL-1/LPS insufflation, GLN pretreated rats had significantly decreased BAL protein and LDH concentrations, but not BAL neutrophil counts, compared to non-GLN pretreated rats. The number of alveolar macrophages and the number of CD163+ macrophages were significantly increased in GLN pretreated IL-1/LPS-insufflated rats compared to non-GLN pretreated, IL-1/LPS-insufflated rats. GLN pretreatment before IL-1/LPS also significantly increased HO-1 concentrations and dephosphorylated p38-MAPK levels but not cytokine levels in alveolar macrophages. Immunofluorescence localized CD163 and HO-1 in alveolar macrophages. CONCLUSION: Short-term GLN pretreatment activates the anti-inflammatory CD163/HO-1/p38-MAPK dephosphorylation pathway of alveolar macrophages and decreases capillary damage but not neutrophil recruitment in IL-1/LPS-insufflated rats.
Type
Journal article
Subject
Acute Lung Injury
Animals
Antigens, CD
Antigens, Differentiation, Myelomonocytic
Bronchoalveolar Lavage Fluid
Capillaries
Glutamine
Heme Oxygenase-1
Interleukin-1
Lipopolysaccharides
Macrophages, Alveolar
Mitogen-Activated Protein Kinases
Phosphorylation
Rats
Rats, Sprague-Dawley
Receptors, Cell Surface
Permalink
https://hdl.handle.net/10161/12988
Published Version (Please cite this version)
10.1371/journal.pone.0130764
Publication Info
Fernandez-Bustamante, Ana; Agazio, Amanda; Wilson, Paul; Elkins, Nancy; Domaleski, Luke; He, Qianbin; ... Repine, John E (2015). Brief Glutamine Pretreatment Increases Alveolar Macrophage CD163/Heme Oxygenase-1/p38-MAPK Dephosphorylation Pathway and Decreases Capillary Damage but Not Neutrophil Recruitment in IL-1/LPS-Insufflated Rats. PLoS One, 10(7). pp. e0130764. 10.1371/journal.pone.0130764. Retrieved from https://hdl.handle.net/10161/12988.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
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Scholars@Duke

Wischmeyer

Paul Edmund Wischmeyer

Professor of Anesthesiology
Paul Wischmeyer M.D., EDIC, FASPEN, FCCM is a critical care, perioperative, and nutrition physician-researcher who specializes in enhancing preparation and recovery from surgery, critical care and COVID-19. He serves as a Tenured Professor of Anesthesiology and Surgery at Duke. He also serves as the Associate Vice Chair for Clinical Research in the Dept. of Anesthesiology and Director of the TPN/Nutrition Team at Duke. Dr. Wischmeyer earned his medical degree with honors at T
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