RESEARCH ARTICLE


Effects of L-amino Acids on Human Peripheral Neutrophil Granulocyte Activation



Sándor Sipka*, 1, Tamás Keresztes2, Ildikó Kovács1, Sándor Sipka Jr2, Sándor Baráth1, Gyula Szegedi1, +, Margit Zeher1, Geza Bruckner3
1 Division of Clinical Immunology, Department of Internal Medicine, University of Debrecen, Hungary
2 Department of Cardiology, University of Debrecen, Hungary
3 Division of Clinical Nutrition, University of Kentucky, KY, USA


© 2014 Sipka et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Division of Clinical Immunology, Department of Internal Medicine, University of Debrecen, 4032 Debrecen, Hungary; Tel/Fax: 3652255-218; E-mail:sipka@iiibel.dote.hu
+ This author has passed away two months ago but he was a member of the team in the Division of Clinical Immunology.


Abstract

Objective:

The objective was to investigate the early (20 minutes) effects of 21 L-amino acids on the activation of human neutrophils and to determine in healthy individuals the effects of a meal on the 1) number and relative luminescence unit (RLU) of peripheral neutrophils, 2) serum glutamate and glucose levels and 3) mTOR signaling network.

Methods:

The RLU of neutrophils stimulated by Ca2+ ionophor (CaI) and phorbol myristate acetate (PMA) following amino acid supplementation (3 x 10-4 M) or after consuming a meal was determined. L-glutamate was measured by HPLC.

Results:

All amino acids resulted in significant inhibitions of neutrophil RLU, except for arginine, which stimulated neutrophils. The ratios of amino acid induced inhibition were significantly higher in the cells stimulated by PMA than by CaI. The consumption of a meal resulted in a significant serum glutamate elevation compared to baseline (2.3 versus 0.9 x10-4 M) 90 minutes after ingestion of the meal. It was independent of the body mass index and returned near fasting levels after 150 minutes. The number of neutrophils was significantly elevated 90 minutes after the meal but the PMA induced RLU was significantly decreased.

Conclusion:

Our ex vivoand in vivoresults suggest that the L-amino acids, independent of their metabolic significance, may continuosly and quickly modify the activity of human peripheral neutrophils, and also the outcome of various immunologic reactions. The activation of the mTORC1 complex likely involves a transient impairment in the function of mTORC2 complex in these processes.

Keywords: L-amino acids, L-glutamate, mTOR, neutrophils, RLU.