Diets enriched in ornithine 2-oxoglutarate (ornithine α-ketoglutarate; OKG) improve immune status during stress. We described previously the ability of OKG to increase the respiratory burst in polymorphonuclear neutrophils (PMNs), but the underlying mechanisms remain unclear. OKG is usually recognized as generating glutamine, arginine and polyamines. The aim of the present study was first to determine the effects of OKG on PMN bactericidal functions (chemotaxis and respiratory burst) in stressed rats, and whether these effects could be reproduced by glutamine- or arginine-enriched diets. Secondly, we investigated the metabolic pathway involved in these actions, using three metabolic inhibitors: methionine sulphoximine (an inhibitor of glutamine synthetase), S-methylthiourea (an inhibitor of inducible nitric oxide synthase) and difluoromethylornithine (an inhibitor of ornithine decarboxylase). OKG, arginine and glutamine all increased the production of reactive oxygen species (evaluated by chemiluminescence, ferricytochrome c reduction and flow cytometry). Only OKG markedly enhanced the chemotaxis index (5-fold). Inhibition of glutamine synthetase showed that glutamine production was not involved in the action of OKG. The use of S-methylthiourea and difluoromethylornithine demonstrated that OKG modulated the respiratory burst via nitric oxide (NO·) and polyamine generation. Moreover, OKG stimulated PMN migration via NO·, but arginine administration failed to reproduce this effect. These data suggest that OKG (or its metabolites) and arginine are channelled differently in PMNs. This hypothesis deserves further study.
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February 11 2002
Effects of ornithine 2-oxoglutarate on neutrophils in stressed rats: evidence for the involvement of nitric oxide and polyamines
Christophe MOINARD;
*Laboratoire de Biochimie, Biologie Moléculaire et Nutrition EA 2416 and Centre de Recherche en Nutrition Humaine, Faculté de Pharmacie, 63001 Clermont-Ferrand, France
†Laboratoire de Biologie de la Nutrition EA2498, Faculté de Pharmacie, 75270 Paris, France
Correspondence: Mr C. Moinard, Laboratoire de Biologie de la Nutrition, Faculté de Pharmacie, 4, avenue de l'Observatoire, 75270 PARIS Cedex 06, France (e-mail [email protected]).
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Florence CALDEFIE;
Florence CALDEFIE
*Laboratoire de Biochimie, Biologie Moléculaire et Nutrition EA 2416 and Centre de Recherche en Nutrition Humaine, Faculté de Pharmacie, 63001 Clermont-Ferrand, France
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Stephane WALRAND;
Stephane WALRAND
*Laboratoire de Biochimie, Biologie Moléculaire et Nutrition EA 2416 and Centre de Recherche en Nutrition Humaine, Faculté de Pharmacie, 63001 Clermont-Ferrand, France
†Laboratoire de Biologie de la Nutrition EA2498, Faculté de Pharmacie, 75270 Paris, France
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Arlette TRIDON;
Arlette TRIDON
‡Laboratoire d'Immunologie, Faculté de Pharmacie, 63001 Clermont-Ferrand, France
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Jacques CHASSAGNE;
Jacques CHASSAGNE
§Laboratoire d'Immunologie, Centre Anti-Cancéreux Jean Perrin, 63000 Clermont-Ferrand, France
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Marie-Paule VASSON;
Marie-Paule VASSON
*Laboratoire de Biochimie, Biologie Moléculaire et Nutrition EA 2416 and Centre de Recherche en Nutrition Humaine, Faculté de Pharmacie, 63001 Clermont-Ferrand, France
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Luc CYNOBER
Luc CYNOBER
†Laboratoire de Biologie de la Nutrition EA2498, Faculté de Pharmacie, 75270 Paris, France
¶Laboratoire de Biochimie, Hotel Dieu, AP-HP et Inserm U341, 75004 Paris, France
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Publisher: Portland Press Ltd
Received:
May 14 2001
Revision Received:
September 10 2001
Accepted:
October 25 2001
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society and the Medical Research Society © 2002
2002
Clin Sci (Lond) (2002) 102 (3): 287–295.
Article history
Received:
May 14 2001
Revision Received:
September 10 2001
Accepted:
October 25 2001
Citation
Christophe MOINARD, Florence CALDEFIE, Stephane WALRAND, Arlette TRIDON, Jacques CHASSAGNE, Marie-Paule VASSON, Luc CYNOBER; Effects of ornithine 2-oxoglutarate on neutrophils in stressed rats: evidence for the involvement of nitric oxide and polyamines. Clin Sci (Lond) 1 March 2002; 102 (3): 287–295. doi: https://doi.org/10.1042/cs1020287
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