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.
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 articleSubject
Acute Lung InjuryAnimals
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
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https://hdl.handle.net/10161/12988Published Version (Please cite this version)
10.1371/journal.pone.0130764Publication 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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Show full item recordScholars@Duke
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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