Endotoxin Tolerance in Abdominal Aortic Aneurysm Macrophages, In Vitro: A Case–Control Study
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...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-09-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/9/9/896 |
| _version_ | 1797553040569401344 |
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| author | Lara T. Meital Mark T. Windsor Alesiya E. Maynard Karl Schulze Rebecca Magee Jill O’Donnell Pankaj Jha Chaim Y. Meital Maria Perissiou Steven Coverdale Jonathan Golledge Anna V. Kuballa Tom G. Bailey Christopher D. Askew Fraser D. Russell |
| author_facet | Lara T. Meital Mark T. Windsor Alesiya E. Maynard Karl Schulze Rebecca Magee Jill O’Donnell Pankaj Jha Chaim Y. Meital Maria Perissiou Steven Coverdale Jonathan Golledge Anna V. Kuballa Tom G. Bailey Christopher D. Askew Fraser D. Russell |
| author_sort | Lara T. Meital |
| collection | DOAJ |
| description | 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; <i>n</i> = 33) and sex-matched control participants (<i>n</i> = 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, <i>p</i> < 0.05; IL-6 3.2 ± 0.6 vs. 1.4 ± 0.3 ng/mL, <i>p</i> < 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. |
| first_indexed | 2024-03-10T16:10:42Z |
| format | Article |
| id | doaj.art-787b14f51e7a4a9fac7bbfac4661c448 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T16:10:42Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-787b14f51e7a4a9fac7bbfac4661c4482023-11-20T14:31:31ZengMDPI AGAntioxidants2076-39212020-09-019989610.3390/antiox9090896Endotoxin Tolerance in Abdominal Aortic Aneurysm Macrophages, In Vitro: A Case–Control StudyLara T. Meital0Mark T. Windsor1Alesiya E. Maynard2Karl Schulze3Rebecca Magee4Jill O’Donnell5Pankaj Jha6Chaim Y. Meital7Maria Perissiou8Steven Coverdale9Jonathan Golledge10Anna V. Kuballa11Tom G. Bailey12Christopher D. Askew13Fraser D. Russell14Centre for Genetics, Ecology & Physiology, School of Health and Sport Sciences, University of the Sunshine Coast, Maroochydore, QLD 4558, AustraliaCentre for Genetics, Ecology & Physiology, School of Health and Sport Sciences, University of the Sunshine Coast, Maroochydore, QLD 4558, AustraliaCentre for Genetics, Ecology & Physiology, School of Health and Sport Sciences, University of the Sunshine Coast, Maroochydore, QLD 4558, AustraliaSunshine Vascular, Buderim, QLD 4556, AustraliaDepartment of Surgery, Sunshine Coast University Hospital, Birtinya, QLD 4575, AustraliaDepartment of Surgery, Sunshine Coast University Hospital, Birtinya, QLD 4575, AustraliaDepartment of Surgery, Sunshine Coast University Hospital, Birtinya, QLD 4575, AustraliaMoffat Beach Family Medical Practice, Moffat Beach, QLD 4551, AustraliaCentre for Genetics, Ecology & Physiology, School of Health and Sport Sciences, University of the Sunshine Coast, Maroochydore, QLD 4558, AustraliaCentre for Genetics, Ecology & Physiology, School of Health and Sport Sciences, University of the Sunshine Coast, Maroochydore, QLD 4558, AustraliaQueensland Research Centre for Peripheral Vascular Disease, College of Medicine and Dentistry, James Cook University, Townsville 4811, AustraliaCentre for Genetics, Ecology & Physiology, School of Health and Sport Sciences, University of the Sunshine Coast, Maroochydore, QLD 4558, AustraliaCentre for Genetics, Ecology & Physiology, School of Health and Sport Sciences, University of the Sunshine Coast, Maroochydore, QLD 4558, AustraliaCentre for Genetics, Ecology & Physiology, School of Health and Sport Sciences, University of the Sunshine Coast, Maroochydore, QLD 4558, AustraliaCentre for Genetics, Ecology & Physiology, School of Health and Sport Sciences, University of the Sunshine Coast, Maroochydore, QLD 4558, AustraliaMacrophages 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; <i>n</i> = 33) and sex-matched control participants (<i>n</i> = 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, <i>p</i> < 0.05; IL-6 3.2 ± 0.6 vs. 1.4 ± 0.3 ng/mL, <i>p</i> < 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.https://www.mdpi.com/2076-3921/9/9/896abdominal aortic aneurysmendotoxin tolerancelipid raftsmacrophagestoll-like receptor 4 (TLR4) |
| spellingShingle | Lara T. Meital Mark T. Windsor Alesiya E. Maynard Karl Schulze Rebecca Magee Jill O’Donnell Pankaj Jha Chaim Y. Meital Maria Perissiou Steven Coverdale Jonathan Golledge Anna V. Kuballa Tom G. Bailey Christopher D. Askew Fraser D. Russell Endotoxin Tolerance in Abdominal Aortic Aneurysm Macrophages, In Vitro: A Case–Control Study Antioxidants abdominal aortic aneurysm endotoxin tolerance lipid rafts macrophages toll-like receptor 4 (TLR4) |
| title | Endotoxin Tolerance in Abdominal Aortic Aneurysm Macrophages, In Vitro: A Case–Control Study |
| title_full | Endotoxin Tolerance in Abdominal Aortic Aneurysm Macrophages, In Vitro: A Case–Control Study |
| title_fullStr | Endotoxin Tolerance in Abdominal Aortic Aneurysm Macrophages, In Vitro: A Case–Control Study |
| title_full_unstemmed | Endotoxin Tolerance in Abdominal Aortic Aneurysm Macrophages, In Vitro: A Case–Control Study |
| title_short | Endotoxin Tolerance in Abdominal Aortic Aneurysm Macrophages, In Vitro: A Case–Control Study |
| title_sort | endotoxin tolerance in abdominal aortic aneurysm macrophages in vitro a case control study |
| topic | abdominal aortic aneurysm endotoxin tolerance lipid rafts macrophages toll-like receptor 4 (TLR4) |
| url | https://www.mdpi.com/2076-3921/9/9/896 |
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