Summary of study ST001835

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001159. The data can be accessed directly via it's Project DOI: 10.21228/M8WH6D This work is supported by NIH grant, U2C- DK119886.

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Study IDST001835
Study TitleUse of Integrated Metabolomics, Transcriptomics, and Signal Protein Profile to Characterize the Effector Function and Associated Metabotype of Polarized Macrophage Phenotypes
Study TypeEx vivo macrophage polarization metabotyping
Study SummaryMacrophages (MΦs) display remarkable plasticity and the ability to activate diverse responses to a host of intracellular and external stimuli. Despite extensive characterization of M1 MΦs and a broad set of M2 MΦs, comprehensive characterization of functional phenotype and associated metabotype driving this diverse MΦ activation remains. Herein, we utilized an ex vivo model to produce six MΦ functional phenotypes. Isolated CD14+ PBMCs were differentiated into resting M0 MΦs, and then polarized into M1 (IFN-γ/LPS), M2a (IL-4/IL-13), M2b (IC/LPS), M2c (IL-10), and M2d (IL-6/LIF) MΦs. The MΦs were profiled using a bioanalyte matrix of four cell surface markers, ~50 secreted proteins, ~800 expressed myeloid genes, and ~450 identified metabolites relative to M0 MΦs. Signal protein and expressed gene profiles grouped the MΦs into inflammatory (M1 and M2b) and wound resolution (M2a, M2c, and M2d) phenotypes; however, each had a unique metabolic profile. While both M1 and M2b MΦs shared metabotype profiles consistent with an inflammatory signature; key differences were observed in the TCA cycle, FAO, and OXPHOS. Additionally, M2a, M2c, and M2d MΦs all profiled as tissue repair MΦs; however, metabotype differences were observed in multiple pathways including hexosamine, polyamine, and fatty acid metabolism. These metabolic and other key functional distinctions suggest phagocytic and proliferative functions for M2a MΦs, and angiogenesis and ECM assembly capabilities for M2b, M2c, and M2d MΦs. By integrating metabolomics into a systems analysis of MΦ phenotypes, we provide the most comprehensive map of MΦ diversity to date, along with the global metabolic shifts that correlate to MΦ functional plasticity in these phenotypes.
Institute
Idaho Veterans Research and Education Foundation
DepartmentResearch
LaboratoryAmmons
Last NameAmmons
First NameMary Cloud
AddressMail Stop 151, Bldg 117, 500 W. Fort St. Boise, Idaho 83702
EmailMaryCloud.AmmonsAnderson@va.gov
Phone208-422-1219
Submit Date2021-06-18
Analysis Type DetailLC-MS
Release Date2021-09-17
Release Version1
Mary Cloud Ammons Mary Cloud Ammons
https://dx.doi.org/10.21228/M8WH6D
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Subject:

Subject ID:SU001912
Subject Type:Human
Subject Species:Homo sapiens
Taxonomy ID:9606
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