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.

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

United States

2016-11-06T18:01:56Z

2015

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.

http://www.ncbi.nlm.nih.gov/pubmed/26147379

PONE-D-14-47188

1932-6203

https://hdl.handle.net/10161/12988

eng

Public Library of Science (PLoS)

PLoS One

10.1371/journal.pone.0130764

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

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.

Journal article

Wischmeyer, Paul E|0000-0002-3369-7911

http://www.ncbi.nlm.nih.gov/pubmed/26147379

e0130764

7

Anesthesiology

Anesthesiology, Critical Care Medicine

Clinical Science Departments

Duke

Duke Clinical Research Institute

Institutes and Centers

School of Medicine

Published online

10