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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]
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Abstract

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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

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