Exosomes derived from monocytes and from endothelial cells mediate monocyte and endothelial cell activation under high d-glucose conditions |
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| Authors: | Tamara Sáez Paul de Vos Jeroen Kuipers Luis Sobrevia Marijke M Faas |
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| Institution: | 1. Immunoendocrinology, Division of Medical Biology, Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, the Netherlands;2. Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago 8330024, Chile;3. Molecular Imaging and Electron Microscopy Department of Cell Biology, University of Groningen, University Medical Center Groningen (UMCG), 9713 AZ, Groningen, the Netherlands;4. Department of Physiology, Faculty of Pharmacy, Universidad de Sevilla, Seville, E-41012, Spain;5. University of Queensland Centre for Clinical Research (UQCCR), Faculty of Medicine and Biomedical Sciences, University of Queensland, Herston, QLD, 4029, Australia;6. Department of Obstetrics and Gynecology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, the Netherlands |
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| Abstract: | Diabetes mellitus type 2 (DMT2) is characterized by hyperglycemia and associated with low grade inflammation affecting both endothelial cells and monocytes. Exosomes are nanovesicles, allow communication between endothelial cells and monocytes and have been associated with diabetic complications. In this study we evaluated whether high glucose can activate monocytes and endothelial cells and whether exosomes play a role in this activation. Moreover, we studied whether endothelial cells and monocytes communicate with each other via exosomes under high and basal glncubation. In the first experiment, monomac 6 cells (MM6) were exposed to high glucose (HG; 25?mmol/L) or to exosomes from MM6 exposed to HG (exoMM6-HG) or basal glucose (5.5?mmol/L) (exoMM6-BG). In the second experiment, MM6 were exposed to exosomes from human umbilical vein endothelial cells (HUVECs) and HUVECs to exosomes from MM6. In the third experiment, MM6 and HUVECs were exposed to a mixture of exosomes from MM6 and HUVECs (exoMix). Cell activation was evaluated by measuring the protein surface expression of intracellular adhesion molecule-1 (ICAM-1) by flow cytometry. HG increased ICAM-1 expression in MM6 and monocytic exosomes from HG or BG shown similar effect in HG and BG MM6 cells. Exosomes from HUVECs increased ICAM-1 expression in MM6 cells, incubated under HG or BG, while also exosomes from MM6 increased ICAM-1 expression in HUVECs incubated under HG or BG. The combination of exosomes from both cell types (exoMixHG or exoMixBG) also increased ICAM-1 expression in both type cells in most conditions. However, the exoMixBG reversed the effect of HG in both MM6 and HUVECs. Our results show that HG activated monocytes and endothelial cells and that exosomes play a role in this HG-induced cell ICAM-1 expression. We hypothesize that during DMT2, exosomes may act as a communication mechanism between monocytes and endothelial cells, inducing and maintaining activating of both cell types in the presence of high glucose. |
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| Keywords: | DMT2 Diabetes mellitus type 2 HUVECs Human umbilical vein endothelial cells MM6 Monomac 6 cell line HG BG MM6-HG MM6 exposed to HG MM6-BG MM6 exposed to BG HUVEC-HG HUVECs exposed to HG HUVEC-BG HUVECs exposed to BG NTA Nanoparticle tracking analysis exoMM6 exosomes derived from MM6 exoHUVEC exosomes derived from HUVECs exoMM6-HG exoMM6 from MM6-HG exoMM6-BG exoMM6 from MM6-BG exoHUVEC-HG exoHUVEC from HUVEC-HG exoHUVEC-BG exoHUVEC from HUVEC-BG exoMix exoMM6 and exoHUVEC exoMix-HG exoMM6 and exoHUVEC from MM6-HG and HUVEC-HG exoMix-BG exoMM6 and exoHUVEC from MM6-BG and HUVEC-BG ICAM-1 Intracellular adhesion molecule type 1 Diabetes mellitus type 2 Hyperglycemia Monocytes Endothelial cells Exosomes ICAM-1 |
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