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Analyzing Ex Vivo Metabolic Flux in Splenic and Cardiac Macrophages and Bone Marrow Monocytes
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Glucose metabolism controls disease-specific signatures of macrophage effector functions

Ryu Watanabe1, Marc Hilhorst1,2, Hui Zhang1

  • 1Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, California, USA.

JCI Insight
|October 19, 2018
PubMed

Insights

Macrophages in blood vessel diseases exhibit distinct functional patterns based on the specific condition, with metabolic fitness influencing their inflammatory roles. This disease-specific macrophage behavior is observable even in circulating monocytes.

Area of Science:

  • Immunology
  • Vascular Biology
  • Metabolic Disease

Background:

  • Macrophages are key players in inflammatory blood vessel diseases, contributing to tissue injury and vascular remodeling.
  • Understanding the specific roles of macrophages in different vascular conditions is crucial for targeted therapies.

Purpose of the Study:

  • To determine if inflammatory macrophages in the vessel wall share a common effector program or display disease-specific functional profiles.
  • To compare the functional and metabolic characteristics of macrophages from patients with coronary artery disease (CAD) and giant cell arteritis (GCA).

Main Methods:

  • Comparative analysis of functional profiles of monocyte-derived macrophages from patients with CAD and GCA.
  • Assessment of cytokine and chemokine production, including T cell chemoattractants, IL-1β, IL-6, and PD-L1.
  • Investigation of metabolic fitness and glucose metabolism in relation to inflammatory function.

Main Results:

  • Macrophages from CAD and GCA patients exhibited distinct disease-specific signatures and metabolic fitness.
  • CAD macrophages were high producers of T cell chemoattractants, IL-1β, IL-6, and PD-L1, linked to increased glucose metabolism.
  • GCA macrophages produced T cell chemoattractants but were low for IL-1β, IL-6, and PD-L1, suggesting different inflammatory pathways.

Conclusions:

  • Monocytes and macrophages contribute to vascular inflammation in disease-specific patterns.
  • Macrophage functional trajectories are influenced by microenvironmental factors like glucose availability.
  • Evidence suggests macrophages possess lineage commitment memory, impacting their inflammatory responses.
Abstract

Keywords:
Cardiovascular diseaseGlucose metabolismMetabolismMonocytesVascular Biology

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