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Systemic Inflammation in Metabolic Syndrome: Increased Platelet and Leukocyte Activation, and Key Role of CX(3)CL1/CX(3)CR1 and CCL2/CCR2 Axes in Arterial Platelet-Proinflammatory Monocyte Adhesion
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 CX(3)CL1/CX(3)CR1 and CCL2/CCR2 chemokine axes. M...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6572270/ https://www.ncbi.nlm.nih.gov/pubmed/31109070 http://dx.doi.org/10.3390/jcm8050708 |
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author | Marques, Patrice Collado, Aida Martinez-Hervás, Sergio Domingo, Elena Benito, Esther Piqueras, Laura Real, José T. Ascaso, Juan F. Sanz, Maria-Jesus |
author_facet | Marques, Patrice Collado, Aida Martinez-Hervás, Sergio Domingo, Elena Benito, Esther Piqueras, Laura Real, José T. Ascaso, Juan F. Sanz, Maria-Jesus |
author_sort | Marques, Patrice |
collection | PubMed |
description | 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 CX(3)CL1/CX(3)CR1 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 CX(3)CR1 expression. ELISA determined the plasma marker levels. Platelet-leukocyte aggregates adhesion to tumor necrosis factor-α (TNFα)-stimulated arterial endothelium and the role of CX(3)CL1/CX(3)CR1 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. CX(3)CR1 up-regulation in platelet-Mon1 monocyte aggregates in metabolic syndrome patients led to increased CX(3)CR1/CCR2-dependent platelet-Mon1 monocyte adhesion to dysfunctional arterial endothelium. Conclusion: We provide evidence of generalized immune activation in metabolic syndrome. Additionally, CX(3)CL1/CX(3)CR1 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. |
format | Online Article Text |
id | pubmed-6572270 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-65722702019-06-18 Systemic Inflammation in Metabolic Syndrome: Increased Platelet and Leukocyte Activation, and Key Role of CX(3)CL1/CX(3)CR1 and CCL2/CCR2 Axes in Arterial Platelet-Proinflammatory Monocyte Adhesion Marques, Patrice Collado, Aida Martinez-Hervás, Sergio Domingo, Elena Benito, Esther Piqueras, Laura Real, José T. Ascaso, Juan F. Sanz, Maria-Jesus J Clin Med Article 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 CX(3)CL1/CX(3)CR1 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 CX(3)CR1 expression. ELISA determined the plasma marker levels. Platelet-leukocyte aggregates adhesion to tumor necrosis factor-α (TNFα)-stimulated arterial endothelium and the role of CX(3)CL1/CX(3)CR1 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. CX(3)CR1 up-regulation in platelet-Mon1 monocyte aggregates in metabolic syndrome patients led to increased CX(3)CR1/CCR2-dependent platelet-Mon1 monocyte adhesion to dysfunctional arterial endothelium. Conclusion: We provide evidence of generalized immune activation in metabolic syndrome. Additionally, CX(3)CL1/CX(3)CR1 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. MDPI 2019-05-18 /pmc/articles/PMC6572270/ /pubmed/31109070 http://dx.doi.org/10.3390/jcm8050708 Text en © 2019 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/). |
spellingShingle | Article Marques, Patrice Collado, Aida Martinez-Hervás, Sergio Domingo, Elena Benito, Esther Piqueras, Laura Real, José T. Ascaso, Juan F. Sanz, Maria-Jesus Systemic Inflammation in Metabolic Syndrome: Increased Platelet and Leukocyte Activation, and Key Role of CX(3)CL1/CX(3)CR1 and CCL2/CCR2 Axes in Arterial Platelet-Proinflammatory Monocyte Adhesion |
title | Systemic Inflammation in Metabolic Syndrome: Increased Platelet and Leukocyte Activation, and Key Role of CX(3)CL1/CX(3)CR1 and CCL2/CCR2 Axes in Arterial Platelet-Proinflammatory Monocyte Adhesion |
title_full | Systemic Inflammation in Metabolic Syndrome: Increased Platelet and Leukocyte Activation, and Key Role of CX(3)CL1/CX(3)CR1 and CCL2/CCR2 Axes in Arterial Platelet-Proinflammatory Monocyte Adhesion |
title_fullStr | Systemic Inflammation in Metabolic Syndrome: Increased Platelet and Leukocyte Activation, and Key Role of CX(3)CL1/CX(3)CR1 and CCL2/CCR2 Axes in Arterial Platelet-Proinflammatory Monocyte Adhesion |
title_full_unstemmed | Systemic Inflammation in Metabolic Syndrome: Increased Platelet and Leukocyte Activation, and Key Role of CX(3)CL1/CX(3)CR1 and CCL2/CCR2 Axes in Arterial Platelet-Proinflammatory Monocyte Adhesion |
title_short | Systemic Inflammation in Metabolic Syndrome: Increased Platelet and Leukocyte Activation, and Key Role of CX(3)CL1/CX(3)CR1 and CCL2/CCR2 Axes in Arterial Platelet-Proinflammatory Monocyte Adhesion |
title_sort | systemic inflammation in metabolic syndrome: increased platelet and leukocyte activation, and key role of cx(3)cl1/cx(3)cr1 and ccl2/ccr2 axes in arterial platelet-proinflammatory monocyte adhesion |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6572270/ https://www.ncbi.nlm.nih.gov/pubmed/31109070 http://dx.doi.org/10.3390/jcm8050708 |
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