Plasma microparticles of sickle patients during crisis or taking hydroxyurea modify endothelium inflammatory properties - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Blood Année : 2020

Plasma microparticles of sickle patients during crisis or taking hydroxyurea modify endothelium inflammatory properties

Yohann Garnier
  • Fonction : Auteur
Séverine Ferdinand
  • Fonction : Auteur
Marie Garnier
  • Fonction : Auteur
Kizzy-Clara Cita
  • Fonction : Auteur
Régine Hierso
  • Fonction : Auteur
Aurélie Claes
  • Fonction : Auteur
  • PersonId : 921894
Philippe Connes
Claudine Lapouméroulie
  • Fonction : Auteur
Nathalie Lemonne
  • Fonction : Auteur
Maryse Etienne-Julan
  • Fonction : Auteur
Wassim El Nemer
Marc Romana

Résumé

Plasma MPs released during crisis in SS patients increase endothelial ICAM-1 levels and neutrophil adhesion. l HU treatment lowers PS exposure on MPs, which abolishes their proinflammatory properties. 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. (Blood. 2020;136(2):247-256

Dates et versions

hal-03091322 , version 1 (04-01-2021)

Identifiants

Citer

Yohann Garnier, Séverine Ferdinand, Marie Garnier, Kizzy-Clara Cita, Régine Hierso, et al.. Plasma microparticles of sickle patients during crisis or taking hydroxyurea modify endothelium inflammatory properties. Blood, 2020, 136 (2), pp.247-256. ⟨10.1182/blood.2020004853⟩. ⟨hal-03091322⟩
24 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More