M. Deller¹, D. Mathioudakis¹, J. Engel¹, M. G. Dehne¹, M. Wolff¹, M. Fuchs², G. J. Scheffer³, J. Mühling^3*

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¹ Clinics of Anaesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Giessen and Marburg, Justus-Liebig-University, Giessen, Germany.
² Dr. Ing. Herbert Knauer GmbH, Berlin, Germany.
³ Department of Anesthesiology, Pain, and Palliative Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
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Abstract: High current findings indicate that a substitution with pyruvate can lead to significant alterations or even improvement in neutrophil immunonutrition. However, it is still unknown which intra-cellular pathways might be involved here. Hence, in this study, we investigated whether preincu-bation with an inhibitor of ·NO-synthase (L-NAME), an ·NO donor (SNAP), an analogue of taurine (beta-alanine), an inhibitor of ornithine-decarboxylase (DFMO) as well as a glutamine-analogue (DON), is able to alter the intragranulocytic metabolic response to pyruvate, here for example studied for neutrophil intracellular amino- and α-keto acid concentrations or important neutrophil immune functions [released myeloperoxidase (MPO), the formation of superoxide anions O2- and hydrogen peroxide (H2O2)]. In summary, the interesting first results presented here showed, that any damage of specific metabolic pathways or mechanisms, which seem directly or indirectly to be involved in relevant pyruvate dependent granulocytic nutrient content or specific cellular tasks, could lead to therapeutically desired, but also to unexpected or even fatal consequences for the affected cells. We therefore continue to believe that pyruvate, irrespective of which exact biochemical mechanisms were involved, in neutrophils may satisfy the substantial metabolic demands for a potent intracellular nutrient.

Keywords: Pyruvate, DON, L-NAME, SNAP, β-Alanine, DFMO, Neutrophil, Amino Acids, α-Keto Acids, Immune Function, Immunonutrition

Cite this paper: Deller, M. , Mathioudakis, D. , Engel, J. , Dehne, M. , Wolff, M. , Fuchs, M. , Scheffer, G. and Mühling, J. (2014) Pyruvate-Dependent Changes in Neutrophil Amino- and Alpha-Keto Acid Profiles or Immunity: Which Mechanisms Are Involved?. Open Journal of Immunology, 4, 157-174. doi: 10.4236/oji.2014.44018.

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