Supplemental glutamine augments phagocytosis and reactive oxygen intermediate production by neutrophils and monocytes from postoperative patients in vitro

Furukawa, Satoshi; Saito, Hideaki; Inoue, T.; Matsuda, Takeshi; Fukatsu, Kazuhiko; Han, Ilsoo; Ikeda, Shigeo; Hidemura, Akio

doi:10.1016/s0899-9007(00)00228-8

Cited by 85 publications

(62 citation statements)

References 24 publications

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“…Recent studies have shown that Gln appears to exert a regulatory influence on inflammatory processes by neutrophils responding to inflammatory and infectious stimuli. In fact, Gln supplementation in vitro enhances both phagocytosis and ROS production in isolated neutrophils (34) and, in vivo, suppresses IL-8 production by neutrophils (35). Inasmuch as an increased IL-8 production (33) and oxidative burst alterations (36) have been reported in circulating neutrophils from CF patients, the Gln intracellular depletion found in our study may explain these alterations.…”

Section: Discussionsupporting

confidence: 59%

Neutrophil Glutamine Deficiency in Relation to Genotype in Children with Cystic Fibrosis

et al. 2006

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Pulmonary disease in cystic fibrosis (CF) is characterized by a chronic neutrophil-dominated inflammation of lung tissue. Inasmuch as some amino acids (AA) play a pivotal role in various aspects of neutrophil metabolism, the aim of this study was to investigate a possible alteration of neutrophil AA metabolism and to evaluate its relation (if any) with the genotype. We performed plasma and neutrophil AA analysis in 26 CF patients with known genotype, 10 patients with non-CF bronchiectasis, and 20 normal subjects. The CF group showed a significant decrease of free intracellular neutrophil glutamine (Gln) content compared with controls and the non-CF bronchiectasis group. In the latter group, levels of neutrophil Gln were significantly lower compared with the controls. Amino acid plasma concentration in non-CF bronchiectasis showed a decrease of Gln and taurine compared with controls. Neutrophil Gln content showed values significantly lower in CF patients with severe mutations (class I, II, and III mutations) compared with mild mutations (class IV and V mutations). Results of our study add further evidence for intrinsic neutrophil alterations that could play an important role in the pathogenesis of chronic pulmonary disease in CF patients. (Pediatr Res 59: 13-16, 2006)

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Section: Discussionsupporting

confidence: 59%

Neutrophil Glutamine Deficiency in Relation to Genotype in Children with Cystic Fibrosis

et al. 2006

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“…Gln is characterized as a functional amino acid because it serves as a precursor for (1) purine and pyrimidine synthesis leading to DNA and RNA synthesis; (2) the production of NADPH for superoxide production in phagocytes; (3) oxidation for energy; and (4) nitric oxide production by macrophages (Newsholme et al, 1999;Furukawa et al, 2000;Pithon-Curi et al, 2004). To our knowledge, the fate of utilized Gln in bovine leukocytes has not been metabolically characterized.…”

Section: Glnmentioning

confidence: 99%

Nutrition, immune function and health of dairy cattle

Ingvartsen

Moyes

2013

Animal

264

214

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The large increase in milk yield and the structural changes in the dairy industry have caused major changes in the housing, feeding and management of the dairy cow. However, while large improvements have occurred in production and efficiency, the disease incidence, based on veterinary records, does not seem to be improved. Earlier reviews have covered critical periods such as the transition period in the cow and its influence on health and immune function, the interplay between the endocrine system and the immune system and nutrition and immune function. Knowledge on these topics is crucial for our understanding of disease risk and our effort to develop health and welfare improving strategies, including proactive management for preventing diseases and reducing the severity of diseases. To build onto this the main purpose of this review will therefore be on the effect of physiological imbalance (PI) on immune function, and to give perspectives for prevention of diseases in the dairy cow through nutrition. To a large extent, the health problems during the periparturient period relate to cows having difficulty in adapting to the nutrient needs for lactation. This may result in PI, a situation where the regulatory mechanisms are insufficient for the animals to function optimally leading to a high risk of a complex of digestive, metabolic and infectious problems. The risk of infectious diseases will be increased if the immune competence is reduced. Nutrition plays a pivotal role in the immune response and the effect of nutrition may be directly through nutrients or indirectly by metabolites, for example, in situations with PI. This review discusses the complex relationships between metabolic status and immune function and how these complex interactions increase the risk of disease during early lactation. A special focus will be placed on the major energetic fuels currently known to be used by immune cells (i.e. glucose, non-esterified fatty acids, beta-hydroxybutyrate and glutamine) and how certain metabolic states, such as degree of negative energy balance and risk of PI, contribute to immunosuppression during the periparturient period. Finally, we will address some issues on disease prevention through nutrition.

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“…In turn, activated PMN synthesize and release a number of pro-inflammatory cytokines, including tumor necrosis factor (TNF), IL-1, IL-6, and IL-8 (1,2). Recent work has shown that glutamine supplementation in vitro enhances both phagocytosis and ROS in isolated PMN (3) and, in vivo, suppresses IL-8 production by PMN (4). This has important consequences, as glutamine appears to exert a regulatory influence on inflammatory processes by PMN responding to inflammatory and infectious stimuli.…”

mentioning

confidence: 99%

Granule Localization of Glutaminase in Human Neutrophils and the Consequence of Glutamine Utilization for Neutrophil Activity

Castell

Vance

Abbott

et al. 2004

Journal of Biological Chemistry

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The provision of glutamine in vivo has been observed to reduce to normal levels the neutrophilia observed after exhaustive exercise and to decrease the neutrophil chemoattractant, interleukin-8. Thus, the role for glutamine in the regulation of inflammatory mediators of human neutrophil activation was investigated. The study sought to establish whether glutamine supplementation in vitro affects neutrophil function at rest and whether glutaminase, the major enzyme that metabolizes glutamine, is present in human polymorphonuclear neutrophils (PMN). During in vitro studies, the addition of 2 mM glutamine increased the respiratory burst of human PMN stimulated with both phorbol myristate acetate (PMA) and formyl-methionyl-leucyl-phenylalanine. These observations were made using a highly sensitive, real time chemiluminescent probe, Pholasin ® . Glutamine alone did not stimulate the release of reactive oxygen species. In a novel finding using glutaminase-specific antibodies in combination with flow cytometry and confocal microscopy, glutaminase was shown to be present on the surface of human PMN. Subcellular fractionation revealed that the enzyme was enriched in the secondary granules and could be released into cell culture medium upon stimulation with PMA. In conclusion, human PMN appeared to utilize glutamine and possess the appropriate glutaminase enzyme for metabolizing glutamine. This may depress some pro-inflammatory factors that occur during prolonged, exhaustive exercise. Human polymorphonuclear neutrophils (PMNs)1 are a major class of the nonspecific immune response against infections. This is due, in part, to their ability to produce toxic forms of reactive oxygen species (ROS), including superoxide anions (O 2 Ϫ ), hydrogen peroxide (H 2 O 2 ), and hydroxyl radicals (OH Ϫ ).The generation of ROS requires the cytosolic NADPH oxidase proteins to form a complex with several of the membranebound parts of the oxidases. Once assembled, direct stimulation of cells results in the release of O 2 . into the extracellular compartment or into phagosomes. In turn, activated PMN synthesize and release a number of pro-inflammatory cytokines, including tumor necrosis factor (TNF), IL-1, IL-6, and IL-8 (1, 2). Recent work has shown that glutamine supplementation in vitro enhances both phagocytosis and ROS in isolated PMN (3) and, in vivo, suppresses IL-8 production by PMN (4). This has important consequences, as glutamine appears to exert a regulatory influence on inflammatory processes by PMN responding to inflammatory and infectious stimuli. For example, PMNs taken from patients with burns (5) or after surgery (6) have been shown to have improved bactericidal activity in vitro when glutamine is added to the culture medium for incubation. Glutamine is an important substrate for some key cells of the immune system, such as macrophages and lymphocytes (7,8). It acts as a nitrogen donor for purine and pyrimidine nucleotide synthesis for new DNA synthesis and for mRNA repair. Although classified as non-essential, recent eviden...

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Supplemental glutamine augments phagocytosis and reactive oxygen intermediate production by neutrophils and monocytes from postoperative patients in vitro

Cited by 85 publications

References 24 publications

Neutrophil Glutamine Deficiency in Relation to Genotype in Children with Cystic Fibrosis

Neutrophil Glutamine Deficiency in Relation to Genotype in Children with Cystic Fibrosis

Nutrition, immune function and health of dairy cattle

Granule Localization of Glutaminase in Human Neutrophils and the Consequence of Glutamine Utilization for Neutrophil Activity

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