Dietary glutamine supplementation increases the activity of peritoneal macrophages and hemopoiesis in early-weaned mice inoculated with Mycobacterium bovis bacillus Calmette-Guérin.
ABSTRACT Infants who are breast-fed have been shown to have a lower incidence of certain infectious diseases compared with formula-fed infants. Glutamine is one of the most abundant amino acids found in maternal milk and it is essential for the function of immune system cells such as macrophages. The purpose of this study was to investigate the effect of glutamine supplementation on the function of peritoneal macrophages and on hemopoiesis in early-weaned mice inoculated with Mycobacterium bovis bacillus Calmette-Guérin (BCG). Mice were weaned at 14 d of age and distributed to 2 groups and fed either a glutamine-free diet (n = 16) or a glutamine-supplemented diet (+Gln) (n = 16). Both diets were isonitrogenous (with addition of a mixture of nonessential amino acids) and isocaloric. At d 21, 2 subgroups of mice (n = 16) were intraperitoneally injected with BCG and all mice were killed at d 28. Plasma, muscle and liver glutamine concentrations and muscle glutamine synthetase activity were not affected by diet or inoculation with BCG. The +Gln diet led to increased leukocyte and lymphocyte counts in the peripheral blood (P < 0.05) and granulocyte and lymphocyte counts in the bone marrow and spleen (P < 0.05). The +Gln diet increased spreading and adhesion capacities, hydrogen peroxide, nitric oxide, and tumor necrosis factor-alpha (TNFalpha) syntheses and the phagocytic and fungicidal activity of peritoneal macrophages (P < 0.05). The interaction between the +Gln diet and BCG inoculation increased the area under the curve of interleukin (IL)-1beta and TNFalpha syntheses (P < 0.05). In conclusion, the intake of glutamine increases the function of peritoneal macrophages and hemopoiesis in early-weaned and BCG-inoculated mice. These data have important implications for the design of breast milk substitutes for human infants.
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ABSTRACT: BACKGROUND AND AIMS: Protein malnutrition affects resistance to infection by impairing the inflammatory response, modifying the function of effector cells, such as macrophages. Recent studies have revealed that glutamine-a non-essential amino acid, which could become conditionally essential in some situations like trauma, infection, post-surgery and sepsis-is able to modulate the synthesis of cytokines. The aim of this study was to evaluate the effect of glutamine on the expression of proteins involved in the nuclear factor-kappa B (NF-κB) signalling pathway of peritoneal macrophages from malnourished mice. METHODS: Two-month-old male Balb/c mice were submitted to protein-energy malnutrition (n = 10) with a low-protein diet containing 2 % protein, whereas control mice (n = 10) were fed a 12 % protein-containing diet. The haemogram and analysis of plasma glutamine and corticosterone were evaluated. Peritoneal macrophages were pre-treated in vitro with glutamine (0, 0.6, 2 and 10 mmol/L) for 24 h and then stimulated with 1.25 μg LPS for 30 min, and the synthesis of TNF-α and IL-1α and the expression of proteins related to the NF-κB pathway were evaluated. RESULTS: Malnourished animals had anaemia, leucopoenia, lower plasma glutamine and increased corticosterone levels. TNF-α production of macrophages stimulated with LPS was significantly lower in cells from malnourished animals when cultivated in supraphysiological (2 and 10 mmol/L) concentrations of glutamine. Further, glutamine has a dose-dependent effect on the activation of macrophages, in both groups, when stimulated with LPS, inducing a decrease in TNF-α and IL-1α production and negatively modulating the NF-κB signalling pathway. CONCLUSIONS: These data lead us to infer that the protein malnutrition state interferes with the activation of macrophages and that higher glutamine concentrations, in vitro, have the capacity to act negatively in the NF-κB signalling pathway.European Journal of Nutrition 08/2012; · 3.13 Impact Factor
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ABSTRACT: Glutamine (Gln) is an important substrate for the innate immune cells including lymphocytes and macrophages. In this report, the effects of alanyl-glutamine dipeptide (Ala-Gln) on the naïve immune system, intestinal integrity and gain performance of early-weaned calves were investigated. Early-weaned Chinese Holstein calves were intravenously administered different dosages of Ala-Gln. The effects of Ala-Gln administration were ascertained by evaluating the blood for naïve T lymphocyte subpopulations, the concentrations of serum IgG, serum IgA and intestinal mucosal secretory IgA (s-IgA), the intestinal integrity, as well as the gain performance. Results demonstrated that intravenous administration of Ala-Gln dipeptide (1.01 g/kg×d(-1)) for 7 days had a positive effect on gain performance, intestinal integrity and the immune system. Calves administered doses of Ala-Gln displayed an improvement in gain performance and health status concurrent with increases in blood CD2(+) and CD4(+) lymphocytes, the ratio of CD4(+)/CD8(+), serum IgA and IgG, intestinal mucosal s-IgA while decreasing the occurrence of diarrhea. Moreover, we found that animals given the effective dose (1.01 g/kg×d(-1)) of Ala-Gln resulted in improved immune status and intestinal integrity relative to those given a lower (0.49 g/kg×d(-1)) or higher dose (1.99 g/kg×d(-1)) of Ala-Gln. These findings suggest that maintaining a certain concentration of plasma and/or tissue glutamine in the early stages of weaning is an effective alternative approach for improvement of growth performance in early-wean calves.Veterinary Immunology and Immunopathology 11/2011; 145(1-2):134-42. · 1.88 Impact Factor
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ABSTRACT: Sepsis is a leading cause of death in intensive care units worldwide. Low availability of glutamine contributes to the catabolic state of sepsis. l-Glutamine supplementation has antioxidant properties and modulates the expression of heat shock proteins (HSPs). This study investigated the effects of oral supplementation with l-glutamine plus l-alanine (GLN+ALA), both in the free form and l-alanyl-l-glutamine dipeptide (DIP), on glutamine-glutathione (GSH) axis and HSPs expression in endotoxemic mice. B6.129F2/J mice were subjected to endotoxemia (lipopolysaccharides from Escherichia coli, 5 mg.kg(-1), LPS group) and orally supplemented for 48 h with either l-glutamine (1 g.kg(-1)) plusl-alanine (0.61 g.kg(-1)) (GLN+ALA-LPS group) or 1.49 g.kg(-1) of DIP (DIP-LPS group). Endotoxemia reduced plasma and muscle glutamine concentrations [relative to CTRL group] which were restored in both GLN+ALA-LPS and DIP-LPS groups (P<.05). In supplemented groups were re-established GSH content and intracellular redox status (GSSG/GSH ratio) in circulating erythrocytes and muscle. Thiobarbituric acid reactive substance was 4-fold in LPS treated mice relative to the untreated CTRL group, and plasma TNF-α and IL-1β levels were attenuated by the supplements. Heat shock proteins 27, 70 and 90 (protein and mRNA) were elevated in the LPS group and were returned to basal levels (relative to CTRL group) in both GLN+ALA-LPS and DIP-LPS groups. Supplementations to endotoxemic mice resulted in up-regulation of GSH reductase, GSH peroxidase and glutamate cysteine ligase mRNA expression in muscle. In conclusion, oral supplementations with GLN+ALA or DIP are effective in reversing the conditions of LPS-induced deleterious impact on glutamine-GSH axis in mice under endotoxemia.The Journal of nutritional biochemistry 03/2014; 25(3):345-52. · 4.29 Impact Factor