Glutamine Administration Modulates Endothelial Progenitor Cell and Lung Injury in Septic Mice

Abstract

This study investigated the effects of glutamine (GLN) administration on circulating endothelial progenitor cells (EPCs) and lung angiopoietin (Ang) gene expressions in polymicrobial sepsis. Mice were randomly assigned to a normal control group (NC), septic saline group (SS), and septic GLN group (SG). All mice were fed with a chow diet. Sepsis was induced by cecal ligation and puncture (CLP). The mice in SS group were injected with saline, whereas SG group administered 0.75 g GLN/kg body weight once via tail vein 1 h after CLP. Mice were killed 24 and 48 h after CLP. Their blood and lungs were collected for further analysis. The results showed that, compared with normal mice, sepsis resulted in higher C-X-C motif chemokine-12, vascular endothelial growth factor, nitric oxide levels, and a higher circulating EPC percentage. In addition, inflammatory cytokine concentrations and Ang-2 gene expression were upregulated in lung tissues. GLN administration enhanced the mobilization of EPC, and downregulated inflammatory cytokine production and the Ang-2 gene expressions in lungs. Histopathological findings showed that the extent of inflammatory lesions of the lung alveolar was less severe in the SG group than the SS group after CLP. Our results suggest that a single dose of intravenous GLN administration after initiation of sepsis promotes the mobilization of circulating EPC, and modulates the balance of Ang-Tie2 axis that may improve the vascular function, ameliorate inflammation, and protect lung injury against polymicrobial sepsis.

Intravenous Arginine Administration Promotes Proangiogenic Cells Mobilization and Attenuates Lung Injury in Mice with Polymicrobial Sepsis

“…Mononuclear cells were first identified and CD34 + /CD133 + /CD309 + -cells were gated. Flow cytometric analysis was carried out in accordance to standard settings on a multicolor BD FACS CantoII flow cytometer (BD Biosciences, San Diego, CA, USA), and data were analyzed with BD FACSDiva™ v6.1.3 software (BD Biosciences, San Diego, CA, USA) as described in the previous report [20]. We presented the value of proangiogenic cells in percentage instead of the absolute number among mononuclear cells because the number of proangiogenic cells in plasma are relatively low.…”

Dietary Supplemental Glutamine Enhances the Percentage of Circulating Endothelial Progenitor Cells in Mice with High-Fat Diet-Induced Obesity Subjected to Hind Limb Ischemia

“…It is considered critical for the differentiation, proliferation, and survival in various types of stem cells [16,17]. Previous studies carried out by our laboratory showed that GLN supplementation promotes EPC mobilization in sepsis [18] and in diabetic mice with limb ischemia [19]. Although obesity also exerts inflammation and oxidative stress in the body, the metabolic alterations are distinct from sepsis and diabetes.…”

What's New in Shock, November 2016?

“…Finally, in an article that combines some of the themes investigated by other scientists in this issue (sepsis, ARDS and a single injection of nutritional compound), Dr. Yeh and colleagues have eloquently demonstrated that glutamine can modify progenitor cell and lung injury in mice exposed to severe infection (20). Their basic science work revealed that an intravenous injection of glutamine after cecal ligation and puncture could promote the mobilization of endothelial progenitor cells, in part due to the release of C-X-C motif chemokine 1, vascular endothelial growth factor and nitric oxide (20).…”

“…Their basic science work revealed that an intravenous injection of glutamine after cecal ligation and puncture could promote the mobilization of endothelial progenitor cells, in part due to the release of C-X-C motif chemokine 1, vascular endothelial growth factor and nitric oxide (20). These effects are associated with improved vascular function, ameliorated inflammation and reduced damage of lung tissues (20).…”

“…Their basic science work revealed that an intravenous injection of glutamine after cecal ligation and puncture could promote the mobilization of endothelial progenitor cells, in part due to the release of C-X-C motif chemokine 1, vascular endothelial growth factor and nitric oxide (20). These effects are associated with improved vascular function, ameliorated inflammation and reduced damage of lung tissues (20). Although the use of glutamine in the critically ill is currently debated, the Shock journal has never shied away from contentious issues that require further investigation in order to elucidate appropriate answers for the scientific and medical community!…”