The effect of sodium thiosulfate on immune cell metabolism during porcine hemorrhage and resuscitation.

Autor: Wolfschmitt EM; Institute of Anesthesiological Pathophysiology and Process Engineering, University Hospital Ulm, Ulm, Germany., Hogg M; Institute of Anesthesiological Pathophysiology and Process Engineering, University Hospital Ulm, Ulm, Germany., Vogt JA; Institute of Anesthesiological Pathophysiology and Process Engineering, University Hospital Ulm, Ulm, Germany., Zink F; Institute of Anesthesiological Pathophysiology and Process Engineering, University Hospital Ulm, Ulm, Germany., Wachter U; Institute of Anesthesiological Pathophysiology and Process Engineering, University Hospital Ulm, Ulm, Germany., Hezel F; Institute of Anesthesiological Pathophysiology and Process Engineering, University Hospital Ulm, Ulm, Germany., Zhang X; Institute of Anesthesiological Pathophysiology and Process Engineering, University Hospital Ulm, Ulm, Germany., Hoffmann A; Institute of Anesthesiological Pathophysiology and Process Engineering, University Hospital Ulm, Ulm, Germany., Gröger M; Institute of Anesthesiological Pathophysiology and Process Engineering, University Hospital Ulm, Ulm, Germany., Hartmann C; Clinic for Anesthesia and Intensive Care, University Hospital Ulm, Ulm, Germany., Gässler H; Department of Anaesthesiology, Intensive Care Medicine, Emergency Medicine and Pain Therapy, Federal Armed Forces Hospital Ulm, Ulm, Germany., Datzmann T; Institute of Anesthesiological Pathophysiology and Process Engineering, University Hospital Ulm, Ulm, Germany.; Clinic for Anesthesia and Intensive Care, University Hospital Ulm, Ulm, Germany., Merz T; Institute of Anesthesiological Pathophysiology and Process Engineering, University Hospital Ulm, Ulm, Germany., Hellmann A; Institute of Analytical and Bioanalytical Chemistry, Ulm University, Ulm, Germany., Kranz C; Institute of Analytical and Bioanalytical Chemistry, Ulm University, Ulm, Germany., Calzia E; Institute of Anesthesiological Pathophysiology and Process Engineering, University Hospital Ulm, Ulm, Germany., Radermacher P; Institute of Anesthesiological Pathophysiology and Process Engineering, University Hospital Ulm, Ulm, Germany., Messerer DAC; Institute of Anesthesiological Pathophysiology and Process Engineering, University Hospital Ulm, Ulm, Germany.; Clinic for Anesthesia and Intensive Care, University Hospital Ulm, Ulm, Germany.; Department of Transfusion Medicine and Hemostaseology, Friedrich-Alexander University Erlangen-Nuremberg, University Hospital Erlangen, Erlangen, Germany.
Jazyk: angličtina
Zdroj: Frontiers in immunology [Front Immunol] 2023 Feb 23; Vol. 14, pp. 1125594. Date of Electronic Publication: 2023 Feb 23 (Print Publication: 2023).
DOI: 10.3389/fimmu.2023.1125594
Abstrakt: Introduction: Sodium thiosulfate (Na 2 S 2 O 3 ), an H 2 S releasing agent, was shown to be organ-protective in experimental hemorrhage. Systemic inflammation activates immune cells, which in turn show cell type-specific metabolic plasticity with modifications of mitochondrial respiratory activity. Since H 2 S can dose-dependently stimulate or inhibit mitochondrial respiration, we investigated the effect of Na 2 S 2 O 3 on immune cell metabolism in a blinded, randomized, controlled, long-term, porcine model of hemorrhage and resuscitation. For this purpose, we developed a Bayesian sampling-based model for 13 C isotope metabolic flux analysis (MFA) utilizing 1,2- 13 C 2 -labeled glucose, 13 C 6 -labeled glucose, and 13 C 5 -labeled glutamine tracers.
Methods: After 3 h of hemorrhage, anesthetized and surgically instrumented swine underwent resuscitation up to a maximum of 68 h. At 2 h of shock, animals randomly received vehicle or Na 2 S 2 O 3 (25 mg/kg/h for 2 h, thereafter 100 mg/kg/h until 24 h after shock). At three time points (prior to shock, 24 h post shock and 64 h post shock) peripheral blood mononuclear cells (PBMCs) and granulocytes were isolated from whole blood, and cells were investigated regarding mitochondrial oxygen consumption (high resolution respirometry), reactive oxygen species production (electron spin resonance) and fluxes within the metabolic network (stable isotope-based MFA).
Results: PBMCs showed significantly higher mitochondrial O 2 uptake and lower O 2 • - production in comparison to granulocytes. We found that in response to Na 2 S 2 O 3 administration, PBMCs but not granulocytes had an increased mitochondrial oxygen consumption combined with a transient reduction of the citrate synthase flux and an increase of acetyl-CoA channeled into other compartments, e.g., for lipid biogenesis.
Conclusion: In a porcine model of hemorrhage and resuscitation, Na 2 S 2 O 3 administration led to increased mitochondrial oxygen consumption combined with stimulation of lipid biogenesis in PBMCs. In contrast, granulocytes remained unaffected. Granulocytes, on the other hand, remained unaffected. O 2 • - concentration in whole blood remained constant during shock and resuscitation, indicating a sufficient anti-oxidative capacity. Overall, our MFA model seems to be is a promising approach for investigating immunometabolism; especially when combined with complementary methods.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer JB declared a past collaboration with the authors E-MW, MG and MH to the handling editor.
(Copyright © 2023 Wolfschmitt, Hogg, Vogt, Zink, Wachter, Hezel, Zhang, Hoffmann, Gröger, Hartmann, Gässler, Datzmann, Merz, Hellmann, Kranz, Calzia, Radermacher and Messerer.)
Databáze: MEDLINE
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