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.
Highlights
Neutrophil granulocytes form an indispensable component of the innate immune system and are the most abundant type of white blood cells in mammals, accounting for close to 60% - 70%
Examples here include the reversible transamination of pyruvate by the alanine aminotransferase, the anaplerotic carboxylation of pyruvate metabolized by pyruvate carboxylase, the “de novo synthesis” of important sugars, amino and α-keto acids or the ability to form energy-rich molecules such as nicotinamide adenine dinucleotide phosphate (NADPH) or guanosine-5'-triphosphate (GTP) from pyruvate-depent pathways, and so on [1]-[6]
The free intracellular amino and α-keto acid concentrations, superoxide anion formation, hydrogen peroxide generation as well as the activity of released myeloperoxidase obtained in the control cells were within normal physiological ranges [14] [24] [25]
Summary
Neutrophil granulocytes form an indispensable component of the innate immune system and are the most abundant type of white blood cells in mammals, accounting for close to 60% - 70%. Being highly motile, they quickly congregate at a focal point of infection, attracted by cytokines expressed by activated endothelial and various other cells. The cell is obviously equipped with an impressive arsenal of metabolic pathways capable of taking on the role of a highly effective immunological weapon. One of the most important biochemical processes in which pyruvate is involved, the conversion of pyruvate by the pyruvate dehydrogenase complex (PDH) to form acetyl-CoA, an important link substrate between the metabolic pathways of glycolysis and the citric acid cycle, was, and not really surprising to the concerned viewer, found in neutrophils [7]-[10]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
