scholarly journals Novel Immune Features of the Systemic Inflammation Associated with Primary Hypercholesterolemia: Changes in Cytokine/Chemokine Profile, Increased Platelet and Leukocyte Activation

2018 ◽  
Vol 8 (1) ◽  
pp. 18
Author(s):  
Aida Collado ◽  
Patrice Marques ◽  
Elena Domingo ◽  
Eva Perello ◽  
Herminia González-Navarro ◽  
...  
Keyword(s):  
Systemic Inflammation ◽  
Immune Cell ◽  
Leukocyte Adhesion ◽  
Flow Chamber ◽  
Enzyme Linked Immunosorbent Assay ◽  
Low Grade ◽  
Leukocyte Activation ◽  
Primary Hypercholesterolemia ◽  
Th17 Lymphocytes ◽  
Arterial Endothelium

Primary hypercholesterolemia (PH) is associated with a low grade systemic inflammation that is likely the main driver of premature atherosclerosis. Accordingly, we characterized the immune cell behaviour in PH and its potential consequences. Whole blood from 22 PH patients and 21 age-matched controls was analysed by flow cytometry to determine the percentage of leukocyte immunophenotypes, activation, and platelet-leukocyte aggregates. Plasma markers were determined by Enzyme-Linked ImmunoSorbent Assay (ELISA). The adhesion of platelet-leukocyte aggregates to tumor necrosis factor-α (TNFα)-stimulated arterial endothelium was investigated using the dynamic model of the parallel-plate flow chamber. PH patients presented greater percentage of Mon 3 monocytes, Th2 and Th17 lymphocytes, activated platelets, and leukocytes than controls. The higher percentages of circulating platelet-neutrophil, monocyte and lymphocyte aggregates in patients caused increased platelet-leukocyte adhesion to dysfunctional arterial endothelium. Circulating CXCL8, CCL2, CX3CL1, and IL-6 levels positively correlated with key lipid features of PH, whereas negative correlations were found for IL-4 and IL-10. We provide the first evidence that increased platelet and leukocyte activation leads to elevated platelet-leukocyte aggregates in PH and augmented arterial leukocyte adhesiveness, a key event in atherogenesis. Accordingly, modulation of immune system behavior might be a powerful target in the control of further cardiovascular disease in PH.

scholarly journals Systemic Inflammation in Metabolic Syndrome: Increased Platelet and Leukocyte Activation, and Key Role of CX3CL1/CX3CR1 and CCL2/CCR2 Axes in Arterial Platelet-Proinflammatory Monocyte Adhesion

2019 ◽  
Vol 8 (5) ◽  
pp. 708 ◽  
Author(s):  
Patrice Marques ◽  
Aida Collado ◽  
Sergio Martinez-Hervás ◽  
Elena Domingo ◽  
Esther Benito ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Systemic Inflammation ◽  
Immune Cell ◽  
Flow Chamber ◽  
Low Grade ◽  
Monocyte Adhesion ◽  
The Metabolic Syndrome ◽  
Factor Α ◽  
Arterial Endothelium

Background: Metabolic syndrome is associated with low-grade systemic inflammation, which is a key driver of premature atherosclerosis. We characterized immune cell behavior in metabolic syndrome, its consequences, and the potential involvement of the CX3CL1/CX3CR1 and CCL2/CCR2 chemokine axes. Methods: Whole blood from 18 patients with metabolic syndrome and 21 age-matched controls was analyzed by flow cytometry to determine the leukocyte immunophenotypes, activation, platelet-leukocyte aggregates, and CX3CR1 expression. ELISA determined the plasma marker levels. Platelet-leukocyte aggregates adhesion to tumor necrosis factor-α (TNFα)-stimulated arterial endothelium and the role of CX3CL1/CX3CR1 and CCL2/CCR2 axes was investigated with the parallel-plate flow chamber. Results: When compared with the controls, the metabolic syndrome patients presented greater percentages of eosinophils, CD3+ T lymphocytes, Mon2/Mon3 monocytes, platelet-eosinophil and -lymphocyte aggregates, activated platelets, neutrophils, eosinophils, monocytes, and CD8+ T cells, but lower percentages of Mon1 monocytes. Patients had increased circulating interleukin-8 (IL-8) and TNFα levels and decreased IL-4. CX3CR1 up-regulation in platelet-Mon1 monocyte aggregates in metabolic syndrome patients led to increased CX3CR1/CCR2-dependent platelet-Mon1 monocyte adhesion to dysfunctional arterial endothelium. Conclusion: We provide evidence of generalized immune activation in metabolic syndrome. Additionally, CX3CL1/CX3CR1 or CCL2/CCR2 axes are potential candidates for therapeutic intervention in cardiovascular disorders in metabolic syndrome patients, as their blockade impairs the augmented arterial platelet-Mon1 monocyte aggregate adhesiveness, which is a key event in atherogenesis.

scholarly journals Oral Unsaturated Fat Load Impairs Postprandial Systemic Inflammation in Primary Hypercholesterolemia Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Aida Collado ◽  
Elena Domingo ◽  
Patrice Marques ◽  
Eva Perello ◽  
Sergio Martínez-Hervás ◽  
...  
Keyword(s):  
Systemic Inflammation ◽  
Leukocyte Adhesion ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lower Percentage ◽  
Low Grade ◽  
Platelet Factor ◽  
Primary Hypercholesterolemia ◽  
Unsaturated Fat ◽  
Postprandial State

Context: Primary hypercholesterolemia (PH) is a lipid disorder characterized by elevated levels of cholesterol and low-density lipoprotein (LDL). Low-grade systemic inflammation is associated with PH, which might explain the higher incidence of cardiovascular diseases in this setting.Objective: To evaluate the effect of an oral unsaturated fat load (OUFL) on different immune parameters and functional consequences in patients with PH in postprandial state.Design: A commercial liquid preparation of long-chain triglycerides (Supracal®; ω6/ω3 ratio >20/1, OUFL) was administered to 20 patients and 10 age-matched controls. Whole blood was collected before (fasting state) and 4 h after administration (postprandial state). Flow cytometry was employed to determine platelet and leukocyte activation, and the levels of circulating platelet-leukocyte aggregates. Soluble markers were determined by ELISA, and the parallel-plate flow chamber was employed to study leukocyte adhesion to the dysfunctional arterial endothelium.Results: The PH group had a lower percentage of activated platelets and circulating type 1 monocytes, and blunted neutrophil activation after the OUFL, accompanied by a significant increase in the percentage of regulatory T lymphocytes. In this group, the OUFL led to a significant impairment of leukocyte adhesion to the dysfunctional [tumor necrosis factor α (TNFα)-stimulated] endothelium and reduced the plasma levels of soluble P-selectin, platelet factor-4 (PF-4)/CXCL4, CXCL8, CCL2, CCL5, and TNFα.Conclusion: The OUFL has a beneficial impact on the pro-thrombotic and pro-inflammatory state of PH patients and might be a promising macronutrient approach to dampen the systemic inflammation associated with PH and the development of further cardiovascular events.

scholarly journals The Olive Oil-Based Lipid Clinoleic Blocks Leukocyte Recruitment and Improves Survival during Systemic Inflammation: A Comparative In Vivo Study of Different Parenteral Lipid Emulsions

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Kirsten Buschmann ◽  
Johannes Poeschl ◽  
Natascha Braach ◽  
Hannes Hudalla ◽  
Navina Kuss ◽  
...  
Keyword(s):  
Fish Oil ◽  
Olive Oil ◽  
Systemic Inflammation ◽  
Leukocyte Adhesion ◽  
Flow Chamber ◽  
Leukocyte Recruitment ◽  
Lipid Emulsions ◽  
Cremaster Muscle ◽  
Anti Inflammatory

Although fish oil-based and olive oil-based lipid emulsions have been shown to exert anti-inflammatory functions, the immunomodulating properties of lipids are still controversial. Therefore, we investigated the anti-inflammatory effect of three different parenterally administered lipid emulsions in vivo: olive oil-based Clinoleic, fish oil-based Smoflipid, and soybean oil-based Lipofundin. We observed leukocyte recruitment in inflamed murine cremaster muscle using intravital microscopy and survival in a murine model of LPS-induced systemic inflammation and analyzed expression of leukocyte and endothelial adhesion molecules. Olive oil-based Clinoleic and fish oil-based Smoflipid profoundly inhibited leukocyte adhesion compared to Lipofundin during LPS-induced inflammation of the murine cremaster muscle. In the trauma model of cremaster muscle inflammation, Lipofundin was the only lipid emulsion that even augmented leukocyte adhesion. In contrast to Smoflipid and Lipofundin, Clinoleic effectively blocked leukocyte recruitment and increased survival during lethal endotoxemia. Flow chamber experiments and analysis of adhesion molecule expression suggest that both endothelial and leukocyte driven mechanisms might contribute to anti-inflammatory effects of Clinoleic. We conclude that the anti-inflammatory properties of Clinoleic are superior to those of Smoflipid and Lipofundin even during systemic inflammation. Thus, these results should stimulate further studies investigating parenteral lipids as an anti-inflammatory strategy in critically ill patients.

TOXICITY OF SPHERICAL AND NEEDLE-SHAPED CALCIUM PHOSPHATE BIONS TO INJURED INTIMA OF THE RAT ABDOMINAL AORTA

2019 ◽  
pp. 80-88
Author(s):  
А.Г. Кутихин ◽  
Д.К. Шишкова ◽  
Е.А. Великанова ◽  
А.В. Миронов ◽  
Е.О. Кривкина ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Calcium Phosphate ◽  
Systemic Inflammation ◽  
Intravenous Administration ◽  
Intimal Hyperplasia ◽  
Mesenchymal Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cytotoxic Action ◽  
Alizarin Red ◽  
Synthetic Phenotype

Цель исследования - оценка токсического действия сферических кальций-фосфатных бионов и игольчатых кальций-фосфатных бионов на предварительно поврежденную интиму аорты крыс. Методика. Токсическое действие сферических кальций-фосфатных бионов и игольчатых кальций-фосфатных бионов на поврежденную интиму брюшной аорты крыс линии Wistar (n = 10 на группу) оценивали путем их однократного внутривенного введения после баллонной ангиопластики с эксплантацией поврежденного участка аорты через 5 нед. Биоптаты анализировали: 1) классическими гистологическими методами (окрашивание гематоксилин-эозином, ализариновым красным, по Вейгерту-ван Гизону и по Расселлу-Мовату); 2) иммунофлюоресцентным окрашиванием криосрезов (сочетанное окрашивание на CD31 и CD34, на CD31 и α-гладкомышечный актин (α-ГМА), на виментин и α-ГМА, на коллаген IV типа и α-ГМА). Для оценки влияния системного воспаления на КФБ-индуцированную эндотелиотоксичность определяли содержание моноцитарного хемоаттрактантного белка (МСР-1/CCL2) и церулоплазмина в сыворотке крови прооперированных крыс посредством иммуноферментного анализа. Результаты. Сферические кальций-фосфатные бионы и игольчатые кальций-фосфатные бионы вызывали выраженную гипертрофию интимы брюшной аорты в 90% (9 из 10 крыс) и 80% случаев (8 из 10 крыс) соответственно, в то время как частота гипертрофии в группе контрольных крыс составила лишь 10% (1 из 10 крыс). Неоинтима при экспозиции интимы брюшной аорты обоим типам бионов характеризовалась переходом фенотипа клеток мезенхимального ряда с контрактильного (α-ГМА-положительные и виментин-отрицательные гладкомышечные клетки) и неактивного (α-ГМА-отрицательные и виментин-положительные фибробласты) на активный синтетический (α-ГМА- и виментин-положительные клетки), что приводило к формированию значительных количеств экстрацеллюлярного матрикса. Внутривенное введение сферических кальций-фосфатных бионов и игольчатых кальций-фосфатных бионов не приводило к изменению уровней МСР-1/CCL2 и церулоплазмина в сыворотке крови, что свидетельствовало об отсутствии их возможного влияния на развитие системного воспалительного ответа. Заключение. Внутривенное введение кальций-фосфатных бионов после повреждения интимы брюшной аорты крыс путем баллонной ангиопластики вызывает развитие гипертрофии интимы, частота и выраженность которой не зависит от формы кальций-фосфатных бионов и которая характеризуется переходом фенотипа клеток мезенхимального ряда из контрактильного/неактивного на активный синтетический. При этом эндотелиотоксическое действие кальций-фосфатных бионов обусловлено их непосредственным воздействием на эндотелий, а не развитием системного воспаления. Purpose. To compare toxicity of spherical calcium phosphate bions (SCPB) and needle-shaped calcium phosphate bions (NCPB) to injured intima of rat aortas. Methods. Toxicity of SCPB and NCPB to injured abdominal aortas of Wistar rats (n = 10 per group) was evaluated using intravenous administration of the bions after balloon angioplasty. Rats were sacrificed five weeks postoperation, and an injured aortic segment was excised. Tissue preparations were stained with hematoxylin and eosin, alizarin red S, Weigert-van Gieson, and Movat’s pentachrome stains. Selected tissue samples were then examined using combined immunofluorescence staining (CD31/CD34, CD31/α-smooth muscle actin (α-SMA), α-SMA/vimentin, and α-SMA/collagen IV). Possible influence of systemic inflammation on CPB-induced endothelial toxicity was assessed by measuring monocyte chemoattractant protein-1 and ceruloplasmin in rat serum using the enzyme-linked immunosorbent assay. Results. Intravenous administration of SCPB or NCPB provoked intimal hyperplasia in 90% (9 of 10) and 80% (8 of 10) of rats vs. 10% (1 of 10) in the control group. The neointima was characterized by a phenotypic switch of mesenchymal cells, i.e. transition of a contractile (α-SMA-positive, vimentin-negative vascular smooth muscle cells) and quiescent (α-SMA-negative vimentin-positive fibroblasts) to an active synthetic phenotype (double-positive cells), which resulted in deposition of the extracellular matrix. Neither SCPB nor NCPB changed serum levels of pro-inflammatory molecules, МСР-1/CCL2, and ceruloplasmin. Conclusions. Intravenous administration of CPB upon balloon-induced vascular injury caused intimal hyperplasia regardless of the CPB shape. Hyperplasia foci were characterized by a switch of mesenchymal cells from a contractile/quiescent to an active synthetic phenotype. Endothelial toxicity of CPBs was defined by their direct cytotoxic action rather than induction of systemic inflammation.

STUDY OF HS-CRP AND TNF-A LEVELS IN COPD PATIENTS ACCOMPANIED WITH CORONARY ARTERY DISEASE

2014 ◽  
pp. 48-56
Author(s):  
Van Thi Tran ◽  
Van Bang Le ◽  
Thị Thu Huong Hoang
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Systemic Inflammation ◽  
Chronic Obstructive ◽  
Low Grade ◽  
Cross Sectional ◽  
Copd Patients ◽  
Coronary Artery Angiography ◽  
Hs Crp ◽  
Artery Disease

Aim: Some studies have linked the present of chronic obstructive oulmonary disease (COPD) to coronary artery disease (CAD). Low grade systemic inflammation occurs in patients with COPD as well as patients with CAD. This study was designed to find out the concentration differences of hs-CRP and TNF-a in patients having both chronic obstructive pulmonary and coronary artery diseases with those having either. Methods: A cross - sectional descriptive study was conducted in 200 patients undergoing a coronary artery angiography in the Heart Institute, Thong Nhat Hospital and 115 People Hospital. COPD was diagnosed using GOLD classification. Result: Our study had shown that the levels of hs-CRP and TNF-a were statistically increased in patients with COPD, CAD as well as in patients who had COPD with CAD (p<0,05). The levels of hs-CRP were higher in CAD than in COPD nad the levels of TNF-a were higher in COPD than in CAD. In patients with COPD and CAD, there were increased the levels of both hs-CRP and TNF-a in serum. Conclusion: Systemic inflammation presents in both COPD and CAD. Key words: hs-CRP, TNF-a, coronary artery disease (CAD).

scholarly journals Interleukin-17 and Th17 Lymphocytes Directly Impair Motoneuron Survival of Wildtype and FUS-ALS Mutant Human iPSCs

2021 ◽  
Vol 22 (15) ◽  
pp. 8042
Author(s):  
Mengmeng Jin ◽  
Katja Akgün ◽  
Tjalf Ziemssen ◽  
Markus Kipp ◽  
Rene Günther ◽  
...  
Keyword(s):  
Motor Neurons ◽  
Th17 Cells ◽  
Immune Cell ◽  
Cell Types ◽  
Positive Control ◽  
Interleukin 17 ◽  
Fused In Sarcoma ◽  
Th17 Lymphocytes ◽  
Human Ipscs ◽  
Als Patients

Amyotrophic lateral sclerosis (ALS) is a progressive disease leading to the degeneration of motor neurons (MNs). Neuroinflammation is involved in the pathogenesis of ALS; however, interactions of specific immune cell types and MNs are not well studied. We recently found a shift toward T helper (Th)1/Th17 cell-mediated, pro-inflammatory immune responses in the peripheral immune system of ALS patients, which positively correlated with disease severity and progression. Whether Th17 cells or their central mediator, Interleukin-17 (IL-17), directly affects human motor neuron survival is currently unknown. Here, we evaluated the contribution of Th17 cells and IL-17 on MN degeneration using the co-culture of iPSC-derived MNs of fused in sarcoma (FUS)-ALS patients and isogenic controls with Th17 lymphocytes derived from ALS patients, healthy controls, and multiple sclerosis (MS) patients (positive control). Only Th17 cells from MS patients induced severe MN degeneration in FUS-ALS as well as in wildtype MNs. Their main effector, IL-17A, yielded in a dose-dependent decline of the viability and neurite length of MNs. Surprisingly, IL-17F did not influence MNs. Importantly, neutralizing IL-17A and anti-IL-17 receptor A treatment reverted all effects of IL-17A. Our results offer compelling evidence that Th17 cells and IL-17A do directly contribute to MN degeneration.

scholarly journals Problems of Pathogenesis and Pathogenetic Therapy of COVID-19 from the Perspective of the General Theory of Pathological Systems (General Pathological Processes)

2021 ◽  
Vol 22 (14) ◽  
pp. 7582
Author(s):  
Evgenii Gusev ◽  
Alexey Sarapultsev ◽  
Desheng Hu ◽  
Valeriy Chereshnev
Keyword(s):  
Systemic Inflammation ◽  
Pathological Process ◽  
The State ◽  
The Other ◽  
Low Grade ◽  
Metabolic Dysfunction ◽  
The Metabolic Syndrome ◽  
Other Hand ◽  
Pathogenetic Therapy ◽  
Fundamental Medicine

The COVID-19 pandemic examines not only the state of actual health care but also the state of fundamental medicine in various countries. Pro-inflammatory processes extend far beyond the classical concepts of inflammation. They manifest themselves in a variety of ways, beginning with extreme physiology, then allostasis at low-grade inflammation, and finally the shockogenic phenomenon of “inflammatory systemic microcirculation”. The pathogenetic core of critical situations, including COVID-19, is this phenomenon. Microcirculatory abnormalities, on the other hand, lie at the heart of a specific type of general pathological process known as systemic inflammation (SI). Systemic inflammatory response, cytokine release, cytokine storm, and thrombo-inflammatory syndrome are all terms that refer to different aspects of SI. As a result, the metabolic syndrome model does not adequately reflect the pathophysiology of persistent low-grade systemic inflammation (ChSLGI). Diseases associated with ChSLGI, on the other hand, are risk factors for a severe COVID-19 course. The review examines the role of hypoxia, metabolic dysfunction, scavenger receptors, and pattern-recognition receptors, as well as the processes of the hemophagocytic syndrome, in the systemic alteration and development of SI in COVID-19.

scholarly journals Fourteen days of smoking cessation improves muscle fatigue resistance and reverses markers of systemic inflammation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mohammad Z. Darabseh ◽  
Thomas M. Maden-Wilkinson ◽  
George Welbourne ◽  
Rob C. I. Wüst ◽  
Nessar Ahmed ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Smoking Cessation ◽  
Muscle Fatigue ◽  
Fatigue Resistance ◽  
Systemic Inflammation ◽  
Muscle Function ◽  
Low Grade ◽  
Skeletal Muscle Function ◽  
Tnf Α

AbstractCigarette smoking has a negative effect on respiratory and skeletal muscle function and is a risk factor for various chronic diseases. To assess the effects of 14 days of smoking cessation on respiratory and skeletal muscle function, markers of inflammation and oxidative stress in humans. Spirometry, skeletal muscle function, circulating carboxyhaemoglobin levels, advanced glycation end products (AGEs), markers of oxidative stress and serum cytokines were measured in 38 non-smokers, and in 48 cigarette smokers at baseline and after 14 days of smoking cessation. Peak expiratory flow (p = 0.004) and forced expiratory volume in 1 s/forced vital capacity (p = 0.037) were lower in smokers compared to non-smokers but did not change significantly after smoking cessation. Smoking cessation increased skeletal muscle fatigue resistance (p < 0.001). Haemoglobin content, haematocrit, carboxyhaemoglobin, total AGEs, malondialdehyde, TNF-α, IL-2, IL-4, IL-6 and IL-10 (p < 0.05) levels were higher, and total antioxidant status (TAS), IL-12p70 and eosinophil numbers were lower (p < 0.05) in smokers. IL-4, IL-6, IL-10 and IL-12p70 had returned towards levels seen in non-smokers after 14 days smoking cessation (p < 0.05), and IL-2 and TNF-α showed a similar pattern but had not yet fully returned to levels seen in non-smokers. Haemoglobin, haematocrit, eosinophil count, AGEs, MDA and TAS did not significantly change with smoking cessation. Two weeks of smoking cessation was accompanied with an improved muscle fatigue resistance and a reduction in low-grade systemic inflammation in smokers.

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