Glutamine Therapy Reduces Inflammation and Extracellular Trap Release in Experimental Acute Respiratory Distress Syndrome of Pulmonary Origin.

Gisele Pena De Oliveira,Eduarda Gabrielle Lopes Martins,Priscilla Christina Olsen,Helena D’Anunciação De Oliveira,Marcelo Marcos Morales,Pedro Leme Silva,Paolo Pelosi,Patricia Rieken Macedo Rocco,Jamil Zola Kitoko,Elvira Maria Saraiva,Felipe Mateus Ornellas,Phillipe De Souza Lima-Gomes,Antônio Galina,Natália Cadaxo Rochael,Heloísa Lopes Dos Santos,Carla Cristina De Araújo,Pâmella Nowaski Lugon

doi:10.3390/nu11040831

Gisele Pena De Oliveira, Eduarda Gabrielle Lopes Martins + Show 15 more

Open Access

https://doi.org/10.3390/nu11040831

Copy DOI

Abstract

The innate immune response plays an important role in the pathophysiology of acute respiratory distress syndrome (ARDS). Glutamine (Gln) decreases lung inflammation in experimental ARDS, but its impact on the formation of extracellular traps (ETs) in the lung is unknown. In a mouse model of endotoxin-induced pulmonary ARDS, the effects of Gln treatment on leukocyte counts and ET content in bronchoalveolar lavage fluid (BALF), inflammatory profile in lung tissue, and lung morphofunction were evaluated in vivo. Furthermore, ET formation, reactive oxygen species (ROS) production, glutathione peroxidase (GPx), and glutathione reductase (GR) activities were tested in vitro. Our in vivo results demonstrated that Gln treatment reduced ET release (as indicated by cell-free-DNA content and myeloperoxidase activity), decreased lung inflammation (reductions in interferon-γ and increases in interleukin-10 levels), and improved lung morpho-function (decreased static lung elastance and alveolar collapse) in comparison with ARDS animals treated with saline. Moreover, Gln reduced ET and ROS formation in BALF cells stimulated with lipopolysaccharide in vitro, but it did not alter GPx or GR activity. In this model of endotoxin-induced pulmonary ARDS, treatment with Gln reduced pulmonary functional and morphological impairment, inflammation, and ET release in the lung.

Highlights

The acute respiratory distress syndrome (ARDS) is characterized by diffuse lung inflammation, which results in endothelial and epithelial damage and a subsequent increase in vascular permeability [1,2].The innate immune response plays an important role in the pathophysiology of ARDS [3]
We evaluated the formation of extracellular traps (ETs) in vitro and the mechanisms that could be involved in the Gln modulation of ETs formation. in vivo, we observed that administration of Gln to animals with endotoxin-induced pulmonary ARDS was associated with a reduction in ET formation and appeared to mitigate lung inflammation and morpho-functional impairment
Our data, obtained in a model of endotoxin-induced pulmonary ARDS, suggests that demonstrated that Gln treatment reduced ET release

Summary

Introduction

The acute respiratory distress syndrome (ARDS) is characterized by diffuse lung inflammation, which results in endothelial and epithelial damage and a subsequent increase in vascular permeability [1,2].The innate immune response plays an important role in the pathophysiology of ARDS [3]. Neutrophil influx into the lungs, which is associated with the severity of ARDS, promotes tissue injury and sustains inflammation [4]. NETs are web-like structures consisting of a decondensed neutrophil chromatin scaffold anchoring antimicrobial proteins, such as neutrophil elastase (NE), myeloperoxidase (MPO), and α-defensins, extruded to the extracellular milieu, which can trap and kill pathogens [7,8]. It may damage lung tissue and, play a role in ARDS pathogenesis [9]. Since no pharmacological approaches are effective in ARDS, modulation of NET formation is an appealing target for adjuvant therapy

Methods

Discussion

Conclusion