Plasma microparticles of sickle patients during crisis or taking hydroxyurea modify endothelium inflammatory properties
- 9 July 2020
- journal article
- research article
- Published by American Society of Hematology in Blood
- Vol. 136 (2), 247-256
- https://doi.org/10.1182/blood.2020004853
Abstract
Microparticles (MPs) are submicron extracellular vesicles exposing phosphatidylserine (PS), detected at high concentration in the circulation of sickle cell anemia (SS) patients. Several groups studied the biological effects of MPs generated ex vivo. Here, we analyzed for the first time the impact of circulating MPs on endothelial cells (ECs) from 60 sickle cell disease (SCD) patients. MPs were collected from SCD patients and compared with MPs isolated from healthy individuals (AA). Other plasma MPs were purified from SS patients before and 2 years after the onset of hydroxyurea (HU) treatment or during a vasoocclusive crisis and at steady-state. Compared with AA MPs, SS MPs increased EC ICAM-1 messenger RNA and protein levels, as well as neutrophil adhesion. We showed that ICAM-1 overexpression was primarily caused by MPs derived from erythrocytes, rather than from platelets, and that it was abolished by MP PS capping using annexin V. MPs from SS patients treated with HU were less efficient to induce a proinflammatory phenotype in ECs compared with MPs collected before therapy. In contrast, MPs released during crisis increased ICAM-1 and neutrophil adhesion levels, in a PS-dependent manner, compared with MPs collected at steady-state. Furthermore, neutrophil adhesion was abolished by a blocking anti-ICAM-1 antibody. Our study provides evidence that MPs play a key role in SCD pathophysiology by triggering a proinflammatory phenotype of ECs. We also uncover a new mode of action for HU and identify potential therapeutics: annexin V and anti-ICAM-1 antibodies.This publication has 70 references indexed in Scilit:
- Microparticles and acute lung injuryAmerican Journal of Physiology-Lung Cellular and Molecular Physiology, 2012
- Erythrocyte plasma membrane–bound ERK1/2 activation promotes ICAM-4–mediated sickle red cell adhesion to endotheliumBlood, 2012
- Monocytic microparticles activate endothelial cells in an IL-1β–dependent mannerBlood, 2011
- CXCL1 and its receptor, CXCR2, mediate murine sickle cell vaso-occlusion during hemolytic transfusion reactionsJCI Insight, 2011
- Microparticles From Human Atherosclerotic Plaques Promote Endothelial ICAM-1–Dependent Monocyte Adhesion and Transendothelial MigrationCirculation Research, 2011
- Heterotypic interactions enabled by polarized neutrophil microdomains mediate thromboinflammatory injuryNature Medicine, 2009
- Endothelial expression of autocrine VEGF upon the uptake of tumor-derived microvesicles containing oncogenic EGFRProceedings of the National Academy of Sciences of the United States of America, 2009
- Microvascular endothelial cells express a phosphatidylserine receptor: a functionally active receptor for phosphatidylserine-positive erythrocytesBlood, 2008
- 99mTc-HYNIC-rh-annexin-V scintigraphy: visual and quantitative evaluation of early treatment-induced apoptosis to predict treatment outcomeNuclear Medicine Communications, 2008
- Sickle cell disease: old discoveries, new concepts, and future promiseJCI Insight, 2007