Metabolic Reprogramming of Mouse Bone Marrow Derived Macrophages Following Erythrophagocytosis.
OXPHOS
blood
lipid accumulation
macrophage metabolism
mitochondrial dysregulation
omics technologies
pentose phosphate pathway
Journal
Frontiers in physiology
ISSN: 1664-042X
Titre abrégé: Front Physiol
Pays: Switzerland
ID NLM: 101549006
Informations de publication
Date de publication:
2020
2020
Historique:
received:
26
02
2020
accepted:
02
04
2020
entrez:
20
5
2020
pubmed:
20
5
2020
medline:
20
5
2020
Statut:
epublish
Résumé
Reticuloendothelial macrophages engulf ∼0.2 trillion senescent erythrocytes daily in a process called erythrophagocytosis (EP). This critical mechanism preserves systemic heme-iron homeostasis by regulating red blood cell (RBC) catabolism and iron recycling. Although extensive work has demonstrated the various effects on macrophage metabolic reprogramming by stimulation with proinflammatory cytokines, little is known about the impact of EP on the macrophage metabolome and proteome. Thus, we performed mass spectrometry-based metabolomics and proteomics analyses of mouse bone marrow-derived macrophages (BMDMs) before and after EP of IgG-coated RBCs. Further, metabolomics was performed on BMDMs incubated with free IgG to ensure that changes to macrophage metabolism were due to opsonized RBCs and not to free IgG binding. Uniformly labeled tracing experiments were conducted on BMDMs in the presence and absence of IgG-coated RBCs to assess the flux of glucose through the pentose phosphate pathway (PPP). In this study, we demonstrate that EP significantly alters amino acid and fatty acid metabolism, the Krebs cycle, OXPHOS, and arachidonate-linoleate metabolism. Increases in levels of amino acids, lipids and oxylipins, heme products, and RBC-derived proteins are noted in BMDMs following EP. Tracing experiments with U-
Identifiants
pubmed: 32425810
doi: 10.3389/fphys.2020.00396
pmc: PMC7204509
doi:
Types de publication
Journal Article
Langues
eng
Pagination
396Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL146442
Pays : United States
Organisme : NIGMS NIH HHS
ID : RM1 GM131968
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI106711
Pays : United States
Organisme : NIH HHS
ID : S10 OD021641
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL148151
Pays : United States
Organisme : NHLBI NIH HHS
ID : R21 HL150032
Pays : United States
Organisme : NHLBI NIH HHS
ID : F31 HL134284
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL133049
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL149714
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL115557
Pays : United States
Informations de copyright
Copyright © 2020 Catala, Youssef, Reisz, Dzieciatkowska, Powers, Marchetti, Karafin, Zimring, Hudson, Hansen, Spitalnik and D’Alessandro.
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