Endotoxin Tolerance in Abdominal Aortic Aneurysm Macrophages, In Vitro: A Case-Control Study.

Autor:	Meital LT; Centre for Genetics, Ecology & Physiology, School of Health and Sport Sciences, University of the Sunshine Coast, Maroochydore, QLD 4558, Australia., Windsor MT; Centre for Genetics, Ecology & Physiology, School of Health and Sport Sciences, University of the Sunshine Coast, Maroochydore, QLD 4558, Australia., Maynard AE; Centre for Genetics, Ecology & Physiology, School of Health and Sport Sciences, University of the Sunshine Coast, Maroochydore, QLD 4558, Australia., Schulze K; Sunshine Vascular, Buderim, QLD 4556, Australia., Magee R; Department of Surgery, Sunshine Coast University Hospital, Birtinya, QLD 4575, Australia., O'Donnell J; Department of Surgery, Sunshine Coast University Hospital, Birtinya, QLD 4575, Australia., Jha P; Department of Surgery, Sunshine Coast University Hospital, Birtinya, QLD 4575, Australia., Meital CY; Moffat Beach Family Medical Practice, Moffat Beach, QLD 4551, Australia., Perissiou M; Centre for Genetics, Ecology & Physiology, School of Health and Sport Sciences, University of the Sunshine Coast, Maroochydore, QLD 4558, Australia., Coverdale S; Centre for Genetics, Ecology & Physiology, School of Health and Sport Sciences, University of the Sunshine Coast, Maroochydore, QLD 4558, Australia.; School of Medicine, Griffith University, Birtinya, QLD 4575, Australia., Golledge J; Queensland Research Centre for Peripheral Vascular Disease, College of Medicine and Dentistry, James Cook University, Townsville 4811, Australia.; Department of Vascular and Endovascular Surgery, Townsville Hospital, Townsville 4810, Australia., Kuballa AV; Centre for Genetics, Ecology & Physiology, School of Health and Sport Sciences, University of the Sunshine Coast, Maroochydore, QLD 4558, Australia., Bailey TG; Centre for Genetics, Ecology & Physiology, School of Health and Sport Sciences, University of the Sunshine Coast, Maroochydore, QLD 4558, Australia.; Centre for Research on Exercise, Physical Activity and Health, School of Human Movement and Nutrition Sciences, The University of Queensland, St. Lucia, QLD 4072, Australia., Askew CD; Centre for Genetics, Ecology & Physiology, School of Health and Sport Sciences, University of the Sunshine Coast, Maroochydore, QLD 4558, Australia., Russell FD; Centre for Genetics, Ecology & Physiology, School of Health and Sport Sciences, University of the Sunshine Coast, Maroochydore, QLD 4558, Australia.
Jazyk:	angličtina
Zdroj:	Antioxidants (Basel, Switzerland) [Antioxidants (Basel)] 2020 Sep 21; Vol. 9 (9). Date of Electronic Publication: 2020 Sep 21.
DOI:	10.3390/antiox9090896
Abstrakt:	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.
Databáze:	MEDLINE
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