Limits...
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 A, Agazio A, Wilson P, Elkins N, Domaleski L, He Q, Baer KA, Moss AF, Wischmeyer PE, Repine JE - PLoS ONE (2015)

Bottom Line: Glutamine (GLN) attenuates acute lung injury (ALI) but its effect on alveolar macrophages is unknown.GLN pretreatment before IL-1/LPS also significantly increased HO-1 concentrations and dephosphorylated p38-MAPK levels but not cytokine levels in alveolar macrophages.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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus

Lung injury features.There was no interaction between GLN pretreatment and IL-1/LPS insufflation on BAL protein concentrations (1a). IL-1/LPS significantly increased BAL protein levels in both GLN+ and GLN- groups. GLN+IL-1/LPS+ groups had significantly lower BAL protein concentrations than GLN-IL-1/LPS+ groups. GLN and IL-1/LPS showed a significant interaction on BAL LDH concentration (1b). BAL LDH concentrations were significantly higher in GLN-IL-1/LPS+ groups compared to both IL-1/LPS- groups. GLN+IL-1/LPS+ rats had significantly lower BAL LDH levels than GLN-IL-1/LPS+ groups. Fig 1c shows representative H&E histology images from each group. IL-1/LPS insufflation increased the blindly assessed histological lung injury scores with no interaction or effect by GLN pretreatment (1d). (The significance of differences among the four groups was analyzed by two-way ANOVA followed by paired comparisons. Statistical significance was accepted as p<0.05: * compared to GLN-IL-1/LPS- group, # compared to respective GLN+IL-1/LPS- group, ^ compared to GLN-IL-1/LPS+ group).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4493112&req=5

pone.0130764.g001: Lung injury features.There was no interaction between GLN pretreatment and IL-1/LPS insufflation on BAL protein concentrations (1a). IL-1/LPS significantly increased BAL protein levels in both GLN+ and GLN- groups. GLN+IL-1/LPS+ groups had significantly lower BAL protein concentrations than GLN-IL-1/LPS+ groups. GLN and IL-1/LPS showed a significant interaction on BAL LDH concentration (1b). BAL LDH concentrations were significantly higher in GLN-IL-1/LPS+ groups compared to both IL-1/LPS- groups. GLN+IL-1/LPS+ rats had significantly lower BAL LDH levels than GLN-IL-1/LPS+ groups. Fig 1c shows representative H&E histology images from each group. IL-1/LPS insufflation increased the blindly assessed histological lung injury scores with no interaction or effect by GLN pretreatment (1d). (The significance of differences among the four groups was analyzed by two-way ANOVA followed by paired comparisons. Statistical significance was accepted as p<0.05: * compared to GLN-IL-1/LPS- group, # compared to respective GLN+IL-1/LPS- group, ^ compared to GLN-IL-1/LPS+ group).

Mentions: No interaction was found between GLN and IL-1/LPS on BAL protein levels. BAL protein concentrations were similar in both non-IL-1/LPS groups (Fig 1a). Following IL-1/LPS, BAL protein concentrations significantly increased compared to non-GLN non-IL-1/LPS rats, but BAL protein levels in the GLN-pretreated IL-1/LPS-insufflated group were significantly lower than in the non-GLN IL-1/LPS-insufflated group.


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 A, Agazio A, Wilson P, Elkins N, Domaleski L, He Q, Baer KA, Moss AF, Wischmeyer PE, Repine JE - PLoS ONE (2015)

Lung injury features.There was no interaction between GLN pretreatment and IL-1/LPS insufflation on BAL protein concentrations (1a). IL-1/LPS significantly increased BAL protein levels in both GLN+ and GLN- groups. GLN+IL-1/LPS+ groups had significantly lower BAL protein concentrations than GLN-IL-1/LPS+ groups. GLN and IL-1/LPS showed a significant interaction on BAL LDH concentration (1b). BAL LDH concentrations were significantly higher in GLN-IL-1/LPS+ groups compared to both IL-1/LPS- groups. GLN+IL-1/LPS+ rats had significantly lower BAL LDH levels than GLN-IL-1/LPS+ groups. Fig 1c shows representative H&E histology images from each group. IL-1/LPS insufflation increased the blindly assessed histological lung injury scores with no interaction or effect by GLN pretreatment (1d). (The significance of differences among the four groups was analyzed by two-way ANOVA followed by paired comparisons. Statistical significance was accepted as p<0.05: * compared to GLN-IL-1/LPS- group, # compared to respective GLN+IL-1/LPS- group, ^ compared to GLN-IL-1/LPS+ group).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4493112&req=5

pone.0130764.g001: Lung injury features.There was no interaction between GLN pretreatment and IL-1/LPS insufflation on BAL protein concentrations (1a). IL-1/LPS significantly increased BAL protein levels in both GLN+ and GLN- groups. GLN+IL-1/LPS+ groups had significantly lower BAL protein concentrations than GLN-IL-1/LPS+ groups. GLN and IL-1/LPS showed a significant interaction on BAL LDH concentration (1b). BAL LDH concentrations were significantly higher in GLN-IL-1/LPS+ groups compared to both IL-1/LPS- groups. GLN+IL-1/LPS+ rats had significantly lower BAL LDH levels than GLN-IL-1/LPS+ groups. Fig 1c shows representative H&E histology images from each group. IL-1/LPS insufflation increased the blindly assessed histological lung injury scores with no interaction or effect by GLN pretreatment (1d). (The significance of differences among the four groups was analyzed by two-way ANOVA followed by paired comparisons. Statistical significance was accepted as p<0.05: * compared to GLN-IL-1/LPS- group, # compared to respective GLN+IL-1/LPS- group, ^ compared to GLN-IL-1/LPS+ group).
Mentions: No interaction was found between GLN and IL-1/LPS on BAL protein levels. BAL protein concentrations were similar in both non-IL-1/LPS groups (Fig 1a). Following IL-1/LPS, BAL protein concentrations significantly increased compared to non-GLN non-IL-1/LPS rats, but BAL protein levels in the GLN-pretreated IL-1/LPS-insufflated group were significantly lower than in the non-GLN IL-1/LPS-insufflated group.

Bottom Line: Glutamine (GLN) attenuates acute lung injury (ALI) but its effect on alveolar macrophages is unknown.GLN pretreatment before IL-1/LPS also significantly increased HO-1 concentrations and dephosphorylated p38-MAPK levels but not cytokine levels in alveolar macrophages.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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus