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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.

dc.contributor.author Fernandez-Bustamante, A
dc.contributor.author Agazio, A
dc.contributor.author Wilson, P
dc.contributor.author Elkins, N
dc.contributor.author Domaleski, L
dc.contributor.author He, Q
dc.contributor.author Baer, KA
dc.contributor.author Moss, AF
dc.contributor.author Wischmeyer, Paul Edmund
dc.contributor.author Repine, JE
dc.coverage.spatial United States
dc.date.accessioned 2016-11-06T18:01:56Z
dc.date.issued 2015
dc.identifier http://www.ncbi.nlm.nih.gov/pubmed/26147379
dc.identifier PONE-D-14-47188
dc.identifier.uri https://hdl.handle.net/10161/12988
dc.description.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.
dc.language eng
dc.relation.ispartof PLoS One
dc.relation.isversionof 10.1371/journal.pone.0130764
dc.subject Acute Lung Injury
dc.subject Animals
dc.subject Antigens, CD
dc.subject Antigens, Differentiation, Myelomonocytic
dc.subject Bronchoalveolar Lavage Fluid
dc.subject Capillaries
dc.subject Glutamine
dc.subject Heme Oxygenase-1
dc.subject Interleukin-1
dc.subject Lipopolysaccharides
dc.subject Macrophages, Alveolar
dc.subject Mitogen-Activated Protein Kinases
dc.subject Phosphorylation
dc.subject Rats
dc.subject Rats, Sprague-Dawley
dc.subject Receptors, Cell Surface
dc.title 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.
dc.type Journal article
pubs.author-url http://www.ncbi.nlm.nih.gov/pubmed/26147379
pubs.begin-page e0130764
pubs.issue 7
pubs.organisational-group Anesthesiology
pubs.organisational-group Anesthesiology, Critical Care Medicine
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Duke
pubs.organisational-group Duke Clinical Research Institute
pubs.organisational-group Institutes and Centers
pubs.organisational-group School of Medicine
pubs.publication-status Published online
pubs.volume 10
dc.identifier.eissn 1932-6203


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