Dependence of neutrophil respiratory burst on their metabolic state in the patients with acute destructive pancreatitis of different severity [Зависимость респираторного взрыва нейтрофилов от состояния их метаболизма у больных с разной степенью тяжести острого деструктивного панкреатита]

Тип публикации: статья из журнала

Год издания: 2018

Идентификатор DOI: 10.15789/1563-0625-2019-1-77-88

Ключевые слова: Chemiluminescence, Enzyme activity, Function, Metabolism, Neutrophils, Pancreatitis, Reactive oxygen species, Respiratory burst, Severity stage

Аннотация: The aim of the study was to investigate a dependence of respiratory burst state in neutrophils on activities of their intracellular enzymes in patients with acute destructive pancreatitis (ADP) of different severity. The study included 50 patients with ADP of moderate (17 cases) and severe degree (33 cases). A group of 47 healthy people was examined as controls. The respiratory burst state was examined in neutrophilic granulocytes by means of chemiluminescence assays. A study of NAD(P)-dependent dehydrogenases activity in blood neutrophils was performed using bioluminescent analysis. We have revealed that a decrease in spontaneous and induced synthesis of superoxide radical by neutrophils was detected in ADP patients, independently of the disease severity. Kinetics of primary ROS synthesis was also impaired in patients with severe ADP. In patients with moderate disorder, the level of secondary ROS synthesis by neutrophils proved to be increased, whereas, in cases of severe disease, a disturbed kinetics of secondary ROS synthesis by neutrophils was detected at a resting state, showing increased synthetic level upon additional induction by zymosan. Metabolism of neutrophils in patients with ADP is characterized by activation of plastic processes (due to the products of the pentose phosphate cycle) and aerobic energy (increased substrate flow intensity in the cycle of tricarboxylic acids). However, NADPH neutrophilic pool in patients with moderate disorder could be additionally supported by enzymatic malic enzyme reactions and NADP-dependent glutamate dehydrogenase. Activation of peroxidation events in patients with severe ADP is revealed, which needs NADPH compensation. The state of energy processes in blood neutrophils in patients with ADP is characterized by lacking changes in glycolytic activity, and increased intensity of substrate flux along tricarboxylic acids cycle. Activity of aerobic processes in patients with moderate disease is maintained by the products of amino acid metabolism (via glutamate dehydrogenase), whereas, in severe ADP it may be provided by products of lipid catabolism. Using correlation analysis, a dependence of respiratory burst of neutrophils on the state of their metabolism was studied. We have found that intensity and kinetics of respiratory burst in the neutrophils of controls depends only on the activity of NADP-dependent dehydrogenases. The changes in cellular metabolic activity in the patients with moderate ADP led to disturbances of their regulatory effect upon the state of neutrophil respiratory burst. In patients with severe disorder, the degree a neutrophil respiratory burst is stimulated by reductive amination of α-ketoglutarate, being, however, inhibited by intracellular peroxidation processes. © 2019, SPb RAACI.

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Издание

Журнал: Medical Immunology (Russia)

Выпуск журнала: Vol. 21, Is. 1

Номера страниц: 77-88

ISSN журнала: 15630625

Издатель: Russian Association of Allergologists and Clinical Immunologists, St. Petersburg Regional Branch (SPb RAACI)

Авторы

  • Savchenko A.A. (Research Institute of Medical Problems of the North, Krasnoyarsk Research Center, Siberian Branch, Russian Academy of Sciences, Krasnoyarsk, Russian Federation, Siberian Federal University, Krasnoyarsk, Russian Federation, Laboratory of Molecular and Cellular Physiology and Pathology, Research Institute of Medical Problems of the North, Krasnoyarsk Research Center, Siberian Branch, Russian Academy of Sciences, Siberian Federal University, Krasnoyarsk, Russian Federation)
  • Borisov A.G. (Research Institute of Medical Problems of the North, Krasnoyarsk Research Center, Siberian Branch, Russian Academy of Sciences, Krasnoyarsk, Russian Federation, V. Voyno-Yasenetsky Krasnoyarsk State Medical University, Krasnoyarsk, Russian Federation, Laboratory of Molecular and Cellular Physiology and Pathology, Research Institute of Medical Problems of the North, Krasnoyarsk Research Center, Siberian Branch, Russian Academy of Sciences, Department of Infections, V. Voyno-Yasenetsky Krasnoyarsk State Medical University, Krasnoyarsk, Russian Federation)
  • Zdzitovetskiy D.E. (V. Voyno-Yasenetsky Krasnoyarsk State Medical University, Krasnoyarsk, Russian Federation, Department of Surgical Diseases, V. Voyno-Yasenetsky Krasnoyarsk State Medical University, Krasnoyarsk, Russian Federation)
  • Medvedev A.Yu. (Research Institute of Medical Problems of the North, Krasnoyarsk Research Center, Siberian Branch, Russian Academy of Sciences, Krasnoyarsk, Russian Federation, Laboratory of Molecular and Cellular Physiology and Pathology, Research Institute of Medical Problems of the North, Krasnoyarsk Research Center, Siberian Branch, Russian Academy of Sciences, Krasnoyarsk, Russian Federation)
  • Gvozdev I.I. (Research Institute of Medical Problems of the North, Krasnoyarsk Research Center, Siberian Branch, Russian Academy of Sciences, Krasnoyarsk, Russian Federation, Laboratory of Molecular and Cellular Physiology and Pathology, Research Institute of Medical Problems of the North, Krasnoyarsk Research Center, Siberian Branch, Russian Academy of Sciences, Krasnoyarsk, Russian Federation)

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