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.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Anesthesiology, University of Colorado SOM, Aurora, Colorado, United States of America; Webb-Waring Center, University of Colorado SOM, Aurora, Colorado, United States of America.
authors.forename: Ana
authors.initials: A
authors.lastname: Fernandez-Bustamante
authors.affiliation: Department of Anesthesiology, University of Colorado SOM, Aurora, Colorado, United States of America; Webb-Waring Center, University of Colorado SOM, Aurora, Colorado, United States of America.
authors.forename: Amanda
authors.initials: A
authors.lastname: Agazio
authors.affiliation: Webb-Waring Center, University of Colorado SOM, Aurora, Colorado, United States of America.
authors.forename: Paul
authors.initials: P
authors.lastname: Wilson
authors.affiliation: Webb-Waring Center, University of Colorado SOM, Aurora, Colorado, United States of America.
authors.forename: Nancy
authors.initials: N
authors.lastname: Elkins
authors.affiliation: Webb-Waring Center, University of Colorado SOM, Aurora, Colorado, United States of America.
authors.forename: Luke
authors.initials: L
authors.lastname: Domaleski
authors.affiliation: Department of Anesthesiology, University of Colorado SOM, Aurora, Colorado, United States of America; Webb-Waring Center, University of Colorado SOM, Aurora, Colorado, United States of America.
authors.forename: Qianbin
authors.initials: Q
authors.lastname: He
authors.affiliation: Webb-Waring Center, University of Colorado SOM, Aurora, Colorado, United States of America.
authors.forename: Kaily A
authors.initials: KA
authors.lastname: Baer
authors.affiliation: Adult and Child Center for Health Outcomes and Delivery Science (ACCORDS), University of Colorado SOM, Aurora, Colorado, United States of America.
authors.forename: Angela F D
authors.initials: AF
authors.lastname: Moss
authors.affiliation: Department of Anesthesiology, University of Colorado SOM, Aurora, Colorado, United States of America.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Wischmeyer
authors.affiliation: Department of Medicine, University of Colorado SOM, Aurora, Colorado, United States of America; Webb-Waring Center, University of Colorado SOM, Aurora, Colorado, United States of America.
authors.forename: John E
authors.initials: JE
authors.lastname: Repine
mesh_terms: D055371:Acute Lung Injury / Q000517:prevention & control; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid; D002196:Capillaries / Q000473:pathology*; D005973:Glutamine / Q000008:administration & dosage / Q000494:pharmacology*; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D007375:Interleukin-1 / Q000008:administration & dosage*; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000378:metabolism*; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D007375:Interleukin-1; D008070:Lipopolysaccharides; D011956:Receptors, Cell Surface; D005973:Glutamine; D051547:Heme Oxygenase-1; D020928:Mitogen-Activated Protein Kinases