[Characteristics of amino acid metabolism in myeloid-derived suppressor cells in septic mice].

Autor:	Ma Y; Institute of Infectious Diseases, Peking University Ditan Teaching Hospital, Beijing 100015, China., Zhang Y; Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China.; Beijing Key Laboratory of Emerging Infectious Diseases, Beijing 100015, China., Li R; Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China.; Beijing Key Laboratory of Emerging Infectious Diseases, Beijing 100015, China., Deng SW; Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China.; Beijing Key Laboratory of Emerging Infectious Diseases, Beijing 100015, China., Qin QS; Institute of Infectious Diseases, Peking University Ditan Teaching Hospital, Beijing 100015, China., Zhu LL; Institute of Infectious Diseases, Peking University Ditan Teaching Hospital, Beijing 100015, China.; Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China.; Beijing Key Laboratory of Emerging Infectious Diseases, Beijing 100015, China.
Jazyk:	čínština
Zdroj:	Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences [Beijing Da Xue Xue Bao Yi Xue Ban] 2022 Jun 18; Vol. 54 (3), pp. 532-540.
Abstrakt:	Objective: To explore the amino acid metabolomics characteristics of myeloid-derived suppressor cells (MDSCs) in mice with sepsis induced by the cecal ligation and puncture (CLP). Methods: The sepsis mouse model was prepared by CLP, and the mice were randomly divided into a sham operation group (sham group, n = 10) and a CLP model group ( n = 10). On the 7th day after the operation, 5 mice were randomly selected from the surviving mice in each group, and the bone marrow MDSCs of the mice were isolated. Bone marrow MDSCs were separated to measure the oxygen consumption rate (OCR) by using Agilent Seahorse XF technology and to detect the contents of intracellular amino acids and oligopeptides through ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) technology. Different metabolites and potential biomarkers were analyzed by univariate statistical analysis and multivariate statistical analysis. The major metabolic pathways were enriched using the small molecular pathway database (SMPDB). Results: The proportion of MDSCs in the bone marrow of CLP group mice (75.53% ± 6.02%) was significantly greater than that of the sham group (43.15%± 7.42%, t = 7.582, P < 0.001), and the basal respiratory rate [(50.03±1.20) pmol/min], maximum respiration rate [(78.07±2.57) pmol/min] and adenosine triphosphate (ATP) production [(25.30±1.21) pmol/min] of MDSCs in the bone marrow of CLP group mice were significantly greater than the basal respiration rate [(34.53±0.96) pmol/min, ( t = 17.41, P < 0.001)], maximum respiration rate [(42.57±1.87) pmol/min, ( t = 19.33, P < 0.001)], and ATP production [(12.63±0.96) pmol/min, ( t = 14.18, P < 0.001)] of sham group. Leucine, threonine, glycine, etc. were potential biomarkers of septic MDSCs (all P < 0.05). The increased amino acids were mainly enriched in metabolic pathways, such as malate-aspartate shuttle, ammonia recovery, alanine metabolism, glutathione metabolism, phenylalanine and tyrosine metabolism, urea cycle, glycine and serine metabolism, β-alanine metabolism, glutamate metabolism, arginine and proline metabolism. Conclusion: The enhanced mitochondrial oxidative phosphorylation, malate-aspartate shuttle and alanine metabolism in MDSCs of CLP mice may provide raw materials for mitochondrial aerobic respiration, thereby promoting the immunosuppressive function of MDSCs. Blocking the above metabolic pathways may reduce the risk of secondary infection in sepsis and improve the prognosis.
Databáze:	MEDLINE
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