Abstract
EVALUATING THE PHENOTYPIC PLASTICITY OF HUMAN MONOCYTE-DERIVED MACROPHAGES IN RESPONSE TO COMMON ENVIRONMENTAL TOXICANTS
Cytotherapy (Oxford, England), Vol.27(5 Supplement), pp.S164-S164
05/2025
DOI: 10.1016/j.jcyt.2025.03.329
Abstract
Interest in macrophages as a cell therapy is growing rapidly for the treatment of stroke, cardiomyopathy, and other indications. These therapies rely on in vitro polarization of macrophages before administration into the patient. While in vitro polarization toward an inflammatory or anti-inflammatory phenotype is effective, macrophages remain plastic and able to adapt to their environment upon transplantation. In this work, we aimed to uncover how in vitro polarized human macrophages would respond to exposure to a mixture of common environmental toxicants, Aroclor 1254. Aroclor 1254 is a mixture of polychlorinated biphenyls that were manufactured and used heavily in building materials and electrical equipment globally until its production was banned in the late 1970s. As a forever chemical, signatures of Aroclor 1254 are still commonly found in buildings, food, and people, where it can significantly alter biological processes.
Primary human monocytes were isolated from leukocyte reduction cones and purified using a monocyte negative selection kit. The monocytes were then differentiated into macrophages using M-CSF and then polarized to M1 (IFNg+LPS), M2a (IL-4), or M2c (Dexamethasone) macrophages. After in vitro polarization, each type of macrophage was challenged with exposure to either vehicle (DMSO) or 10 uM of Aroclor 1254 for 48 hours. Macrophages were then analyzed for changes to surface marker expression, cytokine production, and metabolic profile using a SCENITH assay.
Our results show that acute exposure of in vitro polarized macrophages to Aroclor 1254 significantly alter macrophage phenotype toward an inflammatory state. Specifically, levels of IL-10, CD163, and CD206 (anti-inflammatory markers) dropped significantly while production of inflammatory cytokines, such as IL-8, increased dramatically (Fig. 1A). When we analyzed the metabolic profile of macrophages after exposure to Aroclor 1254, we found they were more dependent on glycolytic processes (Fig. 1B) and less able to adapt to fatty acids or amino acid oxidation as a fuel source (Fig. 1C).
This work demonstrates that in vitro polarized macrophages are highly plastic and the signals they encounter post-transplantation can significantly alter their phenotype. In this work, we specifically showed that acute exposure to a common part of the exposome, polychlorinated biphenyls, can significantly alter the phenotype and secretome of macrophages by inducing an immunometabolic shift.
Details
- Title: Subtitle
- EVALUATING THE PHENOTYPIC PLASTICITY OF HUMAN MONOCYTE-DERIVED MACROPHAGES IN RESPONSE TO COMMON ENVIRONMENTAL TOXICANTS
- Creators
- R. Behan-Bush - University of IowaM.V. Schrodt - University of IowaE. Kilburg - University of IowaJ. Liszewski - University of Iowa, Iowa Technology InstituteL. Bitterlich - National University of Ireland, MaynoothK. English - National University of Ireland, MaynoothA. Klingelhutz - Microbiology and Immunology, University of Iowa Hospitals and Clinics, Iowa City, IA, United StatesJ.A. Ankrum - University of Iowa
- Resource Type
- Abstract
- Publication Details
- Cytotherapy (Oxford, England), Vol.27(5 Supplement), pp.S164-S164
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.jcyt.2025.03.329
- ISSN
- 1465-3249
- Language
- English
- Date published
- 05/2025
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Microbiology and Immunology; Iowa Technology Institute; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
- Record Identifier
- 9984821344702771
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