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Published VersionCC BY V4.0, Open Access
Journal article
Endotoxin Tolerance in Abdominal Aortic Aneurysm Macrophages, In Vitro: A Case–Control Study
Antioxidants, Vol.9(9), pp.1-17
2020
Appears in Cancer Research Cluster Research Collection
Abstract
Macrophages are implicated in the pathogenesis of abdominal aortic aneurysm (AAA). This study examined the environmentally conditioned responses of AAA macrophages to inflammatory stimuli. Plasma-and blood-derived monocytes were separated from the whole blood of patients with AAA (30–45 mm diameter; n = 33) and sex-matched control participants (n = 44). Increased concentrations of pro-inflammatory and pro-oxidant biomarkers were detected in the plasma of AAA patients, consistent with systemic inflammation and oxidative stress. However, in monocyte-derived macrophages, a suppressed cytokine response was observed in AAA compared to the control following stimulation with lipopolysaccharide (LPS) (tumor necrosis factor alpha (TNF-α) 26.9 ± 3.3 vs. 15.5 ± 3.2 ng/mL, p < 0.05; IL-6 3.2 ± 0.6 vs. 1.4 ± 0.3 ng/mL, p < 0.01). LPS-stimulated production of 8-isoprostane, a biomarker of oxidative stress, was also markedly lower in AAA compared to control participants. These findings are consistent with developed tolerance in human AAA macrophages. As Toll-like receptor 4 (TLR4) has been implicated in tolerance, macrophages were examined for changes in TLR4 expression and distribution. Although TLR4 mRNA and protein expression were unaltered in AAA, cytosolic internalization of receptors and lipid rafts was found. These findings suggest the inflamed, pro-oxidant AAA microenvironment favors macrophages with an endotoxin-tolerant-like phenotype characterized by a diminished capacity to produce pro-inflammatory mediators that enhance the immune response.
Details
- Title
- Endotoxin Tolerance in Abdominal Aortic Aneurysm Macrophages, In Vitro: A Case–Control Study
- Authors
- Lara Meital (Author) - University of the Sunshine Coast, Queensland, School of Health and Sport Sciences - LegacyMark Windsor (Author) - University of the Sunshine Coast, Queensland, School of Health and Sport Sciences - LegacyAlesiya Maynard (Author) - University of the Sunshine Coast, Queensland, School of Health and Sport Sciences - LegacyKarl Schulze (Author) - Sunshine VascularRebecca Magee (Author) - Sunshine Coast University HospitalJill O'Donnell (Author) - Sunshine Coast University HospitalPankaj Jha (Author) - Sunshine Coast University HospitalChaim Y Meital (Author) - Moffat Beach Family Medical PracticeMaria-Christina Perissiou (Author) - University of the Sunshine Coast, Queensland, School of Health and Sport Sciences - LegacySteven Coverdale (Author) - University of the Sunshine CoastJonathan Golledge (Author) - James Cook UniversityAnna Kuballa (Author) - University of the Sunshine Coast, Queensland, School of Health and Sport Sciences - LegacyTom Bailey (Author) - University of the Sunshine Coast, Queensland, School of Health and Sport Sciences - LegacyChristopher Askew (Author) - University of the Sunshine Coast, Queensland, School of Health and Sport Sciences - LegacyFraser Russell (Author) - University of the Sunshine Coast, Queensland, GeneCology Research Centre - Legacy
- Publication details
- Antioxidants, Vol.9(9), pp.1-17
- Publisher
- MDPI AG
- Date published
- 2020
- DOI
- 10.3390/antiox9090896
- ISSN
- 2076-3921
- Copyright note
- Copyright © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
- Organisation Unit
- School of Health - Biomedicine; UniSC Clinical Trials Centre; School of Health and Sport Sciences - Legacy; Cancer Research Cluster; School of Health - Sports & Exercise Science; Centre for Bioinnovation; School of Health and Behavioural Sciences - Legacy
- Language
- English
- Record Identifier
- 99478708302621
- Output Type
- Journal article
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