Hostname: page-component-cd9895bd7-dk4vv Total loading time: 0 Render date: 2024-12-25T02:35:59.177Z Has data issue: false hasContentIssue false
  • English
  • Français

Evidence that glutamine modulates respiratory burst in stressed rat polymorphonuclear cells through its metabolism into arginine

Published online by Cambridge University Press:  09 March 2007

Christophe Moinard ,
Florence Caldefie-Chezet ,
Stephane Walrand ,
Marie-Paule Vasson  and
Luc Cynober
Christophe Moinard*
Affiliation:
Laboratoire de Biochimie, Biologie Moléculaire et Nutrition EA 2416 and Centre de Recherche en Nutrition Humaine, Faculté de Pharmacie, Clermont-Ferrand, France Laboratoire de Biologie de la Nutrition, Faculté de Pharmacie, 4 avenue de l'Observatoire, 75270 Paris Cedex 06, France
Florence Caldefie-Chezet
Affiliation:
Laboratoire de Biochimie, Biologie Moléculaire et Nutrition EA 2416 and Centre de Recherche en Nutrition Humaine, Faculté de Pharmacie, Clermont-Ferrand, France
Stephane Walrand
Affiliation:
Laboratoire de Biochimie, Biologie Moléculaire et Nutrition EA 2416 and Centre de Recherche en Nutrition Humaine, Faculté de Pharmacie, Clermont-Ferrand, France Laboratoire de Biologie de la Nutrition, Faculté de Pharmacie, 4 avenue de l'Observatoire, 75270 Paris Cedex 06, France
Marie-Paule Vasson
Affiliation:
Laboratoire de Biochimie, Biologie Moléculaire et Nutrition EA 2416 and Centre de Recherche en Nutrition Humaine, Faculté de Pharmacie, Clermont-Ferrand, France
Luc Cynober
Affiliation:
Laboratoire de Biologie de la Nutrition, Faculté de Pharmacie, 4 avenue de l'Observatoire, 75270 Paris Cedex 06, France Laboratoire de Biochimie, Hotel-Dieu, AP-HP and Inserm U341, France
*
*Corresponding author: Dr C. Moinard, fax +33 1 53 73 97 56, email [email protected]
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Glutamine (GLN) and arginine (ARG) are recognized for their ability to modulate immune cell function. However, the metabolic pathways involved in their action remain unclear. It was recently shown that GLN- or ARG-enriched diets increased radical oxygen species (ROS) production by neutrophils from stressed rats. Since these two amino acids have a tied metabolism, we hypothesized that conversion between GLN and ARG (and its active metabolites NO• and polyamines) might be involved. To test this hypothesis male Sprague–Dawley rats (n 117) were randomized into thirteen groups: rats in eleven groups were rendered catabolic by dexamethasone injection (1·5 mg/kg per d for 5 d) and 6·8 mmol either GLN, ARG or non-essential amino acids (NEAA; glycine, alanine and histidine)/kg per d were given by the enteral route; one group was pair-fed to the treated groups. The regimens of all the groups were rendered isonitrogenous by the addition of NEAA. The last group was not treated and was fed ad libitum. For each supplementation three subgroups were formed, each of which received a specific inhibitor: methionine sulfoximine (inhibitor of GLN synthase; 100 mg/kg per d), S-methylthiourea (inhibitor of inducible NO• synthase (iNOS); 50 mg/kg per d) and difluoromethylornithine (inhibitor of ornithine decarboxylase (ODC); 50 mg/kg per d). Oxidative metabolism, intracellular H2O2, and extracellular O2•- production were measured in unstimulated and phorbol myristate acetate-stimulated polymorphonuclear neutrophils. GLN- and ARG-enriched diets increased respiratory burst by neutrophils (oxidative metabolism of 152 (SEM 24) AND 138 (sem 45) v. 57 (sem 18) mV for GLN-, ARG- and NEAA-enriched diets respectively, P<0·05). In vivo inhibition of iNOS or ODC decreased ROS production induced by GLN and ARG. In vivo inhibition of GLN synthase did not modify the effect of ARG on ROS production. In conclusion, GLN and ARG modulate ROS production in neutrophils from stressed rats by the same pathway involving polyamine and NO• synthesis.

Keywords

GlutamineArgininePolymorphonuclear cellsPolyaminesNitric oxideRespiratory burst
Type
Research Article
Information
British Journal of Nutrition , Volume 88 , Issue 6 , December 2002 , pp. 689 - 695
Copyright
Copyright © The Nutrition Society 2002

References

Alexander, JW (1995) Specific nutrients and the immune response. Nutrition 11, 229–232.Google ScholarPubMed
Ardawi, MSM & Jamal, YS (1990) Glutamine metabolism in skeletal muscle of glucocorticoid-treated rats. Clinical Science 79, 139–147.Google Scholar
Ardawi, MSM & Majzoub, MF (1991) Glutamine metabolism in skeletal muscle of septic rats. Metabolism 40, 155–164.Google ScholarPubMed
Barbul, A (1995) The use of arginine in clinical practice. In Amino Acid Metabolism and Therapy in Health and Nutritional Disease, pp. 361–372 [Cynober, L, editor]. Boca Raton, FL: CRC Press.Google Scholar
Brittenden, J, Heys, SD, Ross, J, Park, KGM & Eremin, O (1994) Nutritional pharmacology: effects of L-arginine on host defences, response to trauma and tumour growth. Clinical Science 86, 123–132.CrossRefGoogle ScholarPubMed
Calder, PC & Yaqoob, P (1999) Glutamine and the immune system. Amino Acids 17, 227–241.CrossRefGoogle ScholarPubMed
Catz, SD, Carreras, MC & Poderoso, JJ (1995) Nitric oxide synthase inhibitors decrease human polymorphonuclear leukocyte luminol-dependent chemioluminescence. Free Radical Biological Medicine 19, 741–748.CrossRefGoogle Scholar
Cynober, L (1989) Amino acid metabolism in thermal burns. Journal of Parenteral and Enteral Nutrition 13, 196–205.CrossRefGoogle ScholarPubMed
Cynober, L, Le Boucher, J & Vasson, MP (1995) Arginine metabolism in mammals. Journal of Nutritional Biochemistry 6, 402–413.CrossRefGoogle Scholar
De Bandt, JP & Cynober, L (1998) Amino acids with anabolic properties. Current Opinion in Clinical Nutrition and Metabolic Care 1, 263–272.Google Scholar
Farges, MC, Berard, MP, Raul, F, Cezard, JP, Joly, B, Davot, P, Vasson, MP & Cynober, L (1999) Oral administration of a glutamine-enriched diet before or after endotoxin challenge in aged rats has limited effects. Journal of Nutrition 129, 1799–1806.CrossRefGoogle ScholarPubMed
Fujii, H, Ichimori, K, Hoshiai, K & Nakazawa, H (1997) Nitric oxide inactivates NADPH oxidase in pig neutrophils by inhibiting its assembling process. Journal of Biological Chemistry 272, 32773–32778.CrossRefGoogle ScholarPubMed
Furukawa, S, Saito, H, Fukatsu, K, Hashiguchi, Y, Inaba, Y, Lin, MT, Inoue, T, Han, I, Matsuda, T & Muto, T (1997) Glutamine-enhanced bacterial killing by neutrophils from postoperative patients. Nutrition 13, 863–869.CrossRefGoogle ScholarPubMed
Furukawa, S, Saito, H, Inoue, T, Matsuda, T, Fukatsu, K, Han, I, Ikeda, S & Hidemura, A (2000) Supplemental glutamine augments phagocytosis and reactive oxygen intermediate production by neutrophils and monocytes from postoperative patients in vitro. Nutrition 16, 323–329.CrossRefGoogle ScholarPubMed
Fürst, P & Stehle, P (1995) Glutamine and glutamine-containing dipeptides. In Amino Acid Metabolism and Therapy in Health and Nutritional Disease, pp. 373–383 [Cynober, LA, editor]. Boca Raton, FL: CRC Press.Google Scholar
Heeneman, S & Deutz, NEP (1993) The effect of 4 days methionine sulfoximine administration on net muscle protein breakdown. Clinical Nutrition 12, 182–190.Google Scholar
Holm, P, Kankaanranta, H, Oja, SS, Knowles, RG & Moilanen, E (1999) No detectable NO synthesis from L-arginine or N(G)-hydroxy-L-arginine in fMLP-stimulated human blood neutrophils despite production of nitrite, nitrate, and citrulline from N(G)-hydroxy-L-arginine. Journal of Leukocyte Biology 66, 127–134.Google Scholar
Jeevanandam, M (1995) Trauma and sepsis. In Amino Acid Metabolism and Therapy in Health and Nutritional Disease, pp. 245–255 [Cynober, L, editor]. Boca Raton, FL: CRC Press.Google Scholar
Kandil, HM, Argenzio, RA, Chen, W, Berschneider, HM, Stiles, AD, Westwick, JK, Rippe, RA, Brenner, DA & Rhoads, JM (1995) L-glutamine and L-asparagine stimulate ODC activity and proliferation in a porcine jejunal enterocyte line. American Journal of Physiology 269, G591–G599.Google Scholar
Lasnier, E, Coudray-Lucas, C, Le Boucher, J, Jardel, A & Cynober, L (1996) Ornithine alpha-ketoglutarate counteracts thymus involution and glutamine depletion in endotoxemic rats. Clinical Nutrition 77, 197–200.CrossRefGoogle Scholar
Le Bricon, T, Cynober, L, Field, CJ & Baracos, VE (1995) Supplemental nutrition with ornithine α-ketoglutarate in rats with cancer-associated cachexia: surgical treatment of the tumor improves efficacy of nutritional support. Journal of Nutrition 125, 2999–3010.Google Scholar
Messina, L, Spampinato, G, Arcidiacono, A, Malaguarnera, L, Pagano, M, Kaminska, B, Kacmarek, L & Messina, A (1992) Polyamine involvement in functional activation of human macrophages. Journal of Leukocyte Biology 52, 585–587.Google Scholar
Minet, R, Villie, F, Marcollet, M, Meynial-Denis, D & Cynober, L (1997) Measurement of glutamine synthase activity in rat muscle by a colorimetric assay. Clinica Chimica Acta 268, 121–132.CrossRefGoogle ScholarPubMed
Minet-Quinard, R, Moinard, C, Villié, F, Walrand, S, Vasson, MP, Chopineau, J & Cynober, L (1999) Kinetic impairment of nitrogen and muscle glutamine metabolisms in old glucocorticoid-treated rats. American Journal of Physiology 276, E558–E564.Google Scholar
Minet-Quinard, R, Moinard, C, Walrand, S, Villie, F, Vasson, MP, Davot, P, Chopineau, J & Cynober, L (2000) Induction of a catabolic state in rats by DEXamethasone: dose or time dependency? Journal of Parenteral and Enteral Nutrition 24, 30–36.Google Scholar
Moffat, FL, Han, T, Li, ZM, Peck, MD, Jy, W, Ahn, YS, Chu, AJ & Bourguignon, LYW (1996) Supplemental L-arginine HCl augments bacterial phagocytosis in human polymorphonuclear leukocytes. Journal of Cell Physiology 168, 26–33.3.0.CO;2-A>CrossRefGoogle ScholarPubMed
Moinard, C, Caldefie, F, Walrand, S, Felgines, C, Vasson, MP & Cynober, L (2000) Involvement of glutamine, arginine and polyamines in the action of ornithine α-ketoglutarate on macrophage functions in stressed rats. Journal of Leukocyte Biology 67, 834–840.Google Scholar
Moinard, C, Caldefie, F, Walrand, S, Tridon, A, Chassagne, J, Vasson, MP & Cynober, L (2002) Effects of ornithine 2-oxoglutarate on neutrophils in stressed rats: evidence for the involvement of nitric oxide and polyamines. Clinical Science 102, 287–295.CrossRefGoogle ScholarPubMed
Moinard, C, Chauveau, B, Walrand, S, Felgines, C, Chassagne, J, Caldefie, F, Cynober, LA & Vasson, MP (1999) Phagocyte functions in stressed rats: modulation by glutamine, arginine and ornithine 2-oxoglutarate compared. Clinical Science 97, 59–65.CrossRefGoogle Scholar
Morgan, DML (1994) Difluoromethylornithine (DFMO), an inhibitor of nitrite production by macrophages? Biochemical Society Transactions 22, 389S.CrossRefGoogle ScholarPubMed
Murphy, C & Newsholme, P (1998) Importance of glutamine metabolism in murine macrophages and human monocytes to L-arginine biosynthesis and rates of nitrite or urea production. Clinical Science 95, 397–407.CrossRefGoogle ScholarPubMed
Newsholme, EA, Newsholme, P, Curi, R, Challoner, E & Ardawi, MSM (1988) A role for muscle in the immune system and its importance in surgery, trauma, sepsis and burns. Nutrition 4, 261–268.Google Scholar
Nsi-Emvo, E, Chaton, B, Foltzer-Jourdainne, C, Gosse, F & Raul, F (1996) Premature expression of sucrase-isomaltase triggered by cortocoid-dependent changes in polyamine metabolism. American Journal of Physiology 270, G54–G59.Google Scholar
Odedra, BR, Bates, PC & Millward, DJ (1983) Time course effect of catabolic doses of corticosterone on protein turnover in rat skeletal muscle and liver. Biochemical Journal 214, 617–627.Google Scholar
O'Dowd, Y & Newsholme, P (1997) Evidence for the involvement of glutamine in nitric oxide production by immunostimulated neutrophils. Biochemical Society Transactions 25, 403S.Google Scholar
Parry-Billings, M, Leighton, B, Dimitriadis, GD, Bond, J & Newsholme, EA (1990) Effects of physiological and pathological levels of glucocorticoids on skeletal muscle glutamine metabolism in the rat. Biochemical Pharmacology 40, 1145–1148.CrossRefGoogle ScholarPubMed
Pastores, SM, Kvetan, V & Katz, DP (1994) Immunomodulatory effects and therapeutic potential of glutamine in the critically ill surgical patient. Nutrition 10, 385–391.Google ScholarPubMed
Pieper, GM, Clarke, GA & Gross, GJ (1994) Stimulatory and inhibitory action of nitric oxide donor agents. v. nitrovasodilators on reactive oxygen production by isolated polymorphonuclear leukocytes. Journal of Pharmacological and Experimental Therapy 269, 451–456.Google Scholar
Pithon Curi, TC, De Melo, MP, De Azevedo, RB, Zorn, TMT & Curi, R (1997) Glutamine utilization by rat neutrophils: presence of a phosphate-dependent glutaminase. American Journal of Physiology 273, C1124–C1129.Google Scholar
Raul, F, Gosse, F, Galluser, M, Hasselmann, M & Seiler, N (1995) Functional and metabolic changes in intestine mucosa of rats after enteral administration of ornithine alpha-ketoglutarate salt. Journal of Parenteral and Enteral Nutrition 19, 145–150.Google Scholar
Robinson, LE, Bussière, FI, Le Boucher, J, Farges, MC, Baracos, VE, Cynober, LA & Field, CJ (1999) Amino acid nutrition and immune function in tumor bearing rats: a comparison of glutamine-, arginine- and ornithine α-ketoglutarate-supplemented diets. Clinical Science 97, 657–669.CrossRefGoogle Scholar
Ruetten, H & Thiemermann, C (1996) Prevention of the expression of inducible nitric oxide synthase by aminoguanidine or aminoethyl-isothiourea in macrophages and in the rat. Biochemical and Biophysical Research Communications 225, 525–530.CrossRefGoogle ScholarPubMed
Seth, P, Kumari, R, Dikshit, M & Srimal, RC (1994) Modulation of rat peripheral polymorphonuclear leukocyte response by nitric oxide and arginine. Blood 84, 2741–2748.CrossRefGoogle ScholarPubMed
Shijo, H, Iwabuchi, K, Hosoda, S, Watanabe, H, Nagaoka, I & Sakakibara, N (1998) Evaluation of neutrophil functions after experimental abdominal surgical trauma. Inflammation Research 47, 67–74.CrossRefGoogle ScholarPubMed
Vasson, MP, Roch-Arveiller, M, Couderc, R, Baguet, JC & Raichvarg, D (1994) Effects of alpha-1 acid glycoprotein on human polymorphonuclear neutrophils: influence of glycan microheterogeneity. Clinica Chimica Acta 224, 65–71.Google Scholar
Walters, JD, Cario, AC, Danne, MM & Marucha, PT (1998) An inhibitor of ornithine decarboxylase antagonizes superoxide generation by primed human polymorphonuclear leukocytes. Journal of Inflammation 48, 40–46.Google Scholar
Wu, G, Meininger, CJ, Knabe, DA, Bazer, FW & Rhoads, JM (2000) Arginine nutrition in development, health and disease. Current Opinion in Clinical Nutrition and Metabolic Care 3, 59–66.Google Scholar