TY - JOUR

T1 - Changes in the Phenotype and Metabolism of Peritoneal Macrophages in Mucin-2 Knockout Mice and Partial Restoration of Their Functions In Vitro After L-Fucose Treatment

AU - Arzhanova, Elena L.

AU - Makusheva, Yulia

AU - Pershina, Elena G.

AU - Medvedeva, Snezhanna S.

AU - Litvinova, Ekaterina A.

N1 - Funding This research was funded by the Institute of Cytology and Genetics (FWNR-2022-0015).

PY - 2024/12/24

Y1 - 2024/12/24

N2 - In the development of inflammatory bowel disease (IBD), peritoneal macrophages contribute to the resident intestinal macrophage pool. Previous studies have demonstrated that oral administration of L-fucose exerts an immunomodulatory effect and repolarizes the peritoneal macrophages in vivo in mice. In this study, we analyzed the phenotype and metabolic profile of the peritoneal macrophages from Muc2−/− mice, as well as the effect of L-fucose on the metabolic and morphological characteristics of these macrophages in vitro. The investigation utilized flow cytometry, quantitative PCR (qPCR), measurement of the intracellular ATP and Ca2+ concentrations, an analysis of mitochondrial respiration and membrane potential, and transmission electron microscopy (TEM) for ultrastructural evaluations. The Muc2−/− mice exhibited lower intracellular ATP and Ca2+ levels in their peritoneal macrophages, a higher percentage of stellate macrophages, and an increased oxygen consumption rate (OCR), combined with a higher percentage of mitochondria displaying an abnormal ultrastructure. Additionally, there was a five-fold increase in condensed mitochondria compared to their level in C57BL/6 mice. The number of CD209+ peritoneal macrophages was reduced three-fold, while the number of M1-like cells increased two-fold in the Muc2−/− mice. L-fucose treatment enhanced ATP production and reduced the expression of the Parp1, Mt-Nd2, and Mt-Nd6 genes, which may suggest a reduction in pro-inflammatory factor production and a shift in the differentiation of peritoneal macrophages towards the M2 phenotype.

AB - In the development of inflammatory bowel disease (IBD), peritoneal macrophages contribute to the resident intestinal macrophage pool. Previous studies have demonstrated that oral administration of L-fucose exerts an immunomodulatory effect and repolarizes the peritoneal macrophages in vivo in mice. In this study, we analyzed the phenotype and metabolic profile of the peritoneal macrophages from Muc2−/− mice, as well as the effect of L-fucose on the metabolic and morphological characteristics of these macrophages in vitro. The investigation utilized flow cytometry, quantitative PCR (qPCR), measurement of the intracellular ATP and Ca2+ concentrations, an analysis of mitochondrial respiration and membrane potential, and transmission electron microscopy (TEM) for ultrastructural evaluations. The Muc2−/− mice exhibited lower intracellular ATP and Ca2+ levels in their peritoneal macrophages, a higher percentage of stellate macrophages, and an increased oxygen consumption rate (OCR), combined with a higher percentage of mitochondria displaying an abnormal ultrastructure. Additionally, there was a five-fold increase in condensed mitochondria compared to their level in C57BL/6 mice. The number of CD209+ peritoneal macrophages was reduced three-fold, while the number of M1-like cells increased two-fold in the Muc2−/− mice. L-fucose treatment enhanced ATP production and reduced the expression of the Parp1, Mt-Nd2, and Mt-Nd6 genes, which may suggest a reduction in pro-inflammatory factor production and a shift in the differentiation of peritoneal macrophages towards the M2 phenotype.

KW - fucose

KW - inflammatory bowel disease

KW - macrophages

KW - mucin-2

UR - https://www.mendeley.com/catalogue/e0a4dfca-284c-3a63-b735-41ac07cb0bbb/

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85214487006&origin=inward&txGid=7dcaaa5f7fb38fb3245335107fb8af3f

U2 - 10.3390/ijms26010013

DO - 10.3390/ijms26010013

M3 - статья

VL - 26

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 1

M1 - 113

ER -