Titre :

Intravascular hemolysis activates complement via cell-free heme and heme-loaded microvesicles.

Auteur(s) :

Merle Nicolas, S [Auteur]
Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)]
Grunenwald, Anne [Auteur]
Lille Neurosciences & Cognition - U 1172 [LilNCog]
Rajaratnam, Helena [Auteur]
Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)]
Gnemmi, Viviane [Auteur]
Lille Neurosciences & Cognition - U 1172 [LilNCog]
Frimat, Marie [Auteur]
Lille Inflammation Research International Center (LIRIC) - U995
Figueres, Marie-Lucile [Auteur]
Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)]
Knockaert, Samantha [Auteur]
Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)]
Bouzekri, Sanah [Auteur]
Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)]
Charue, Dominique [Auteur]
Paris-Centre de Recherche Cardiovasculaire [PARCC - UMR-S U970]
Noe, Remi [Auteur]
Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)]
Robe-Rybkine, Tania [Auteur]
Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)]
Le-Hoang, Marie [Auteur]
Paris-Centre de Recherche Cardiovasculaire [PARCC (UMR_S 970/ U970)]
Brinkman, Nathan [Auteur]
Gentinetta, Thomas [Auteur]
Edler, Monika [Auteur]
Petrillo, Sara [Auteur]
Tolosano, Emanuela [Auteur]
Miescher, Sylvia [Auteur]
Le Jeune, Sylvain [Auteur]
Houillier, Pascal [Auteur]
Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)]
Chauvet, Sophie [Auteur]
Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)]
Rabant, Marion [Auteur]
Dimitrov Jordan, D [Auteur]
Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)]
Fremeaux-Bacchi, Veronique [Auteur]
Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)]
Blanc-Brude Olivier, P [Auteur]
Paris-Centre de Recherche Cardiovasculaire [PARCC (UMR_S 970/ U970)]
Roumenina Lubka, T [Auteur]
Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)]

Titre de la revue :

JCI Insight

Nom court de la revue :

JCI Insight

Numéro :

3

Date de publication :

2018-06-21

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

In hemolytic diseases, such as sickle cell disease (SCD), intravascular hemolysis results in the release of hemoglobin, heme, and heme-loaded membrane microvesicles in the bloodstream. Intravascular hemolysis is thus ...
Lire la suite >In hemolytic diseases, such as sickle cell disease (SCD), intravascular hemolysis results in the release of hemoglobin, heme, and heme-loaded membrane microvesicles in the bloodstream. Intravascular hemolysis is thus associated with inflammation and organ injury. Complement system can be activated by heme in vitro. We investigated the mechanisms by which hemolysis and red blood cell (RBC) degradation products trigger complement activation in vivo. In kidney biopsies of SCD nephropathy patients and a mouse model with SCD, we detected tissue deposits of complement C3 and C5b-9. Moreover, drug-induced intravascular hemolysis or injection of heme or hemoglobin in mice triggered C3 deposition, primarily in kidneys. Renal injury markers (Kim-1, NGAL) were attenuated in C3-/- hemolytic mice. RBC degradation products, such as heme-loaded microvesicles and heme, induced alternative and terminal complement pathway activation in sera and on endothelial surfaces, in contrast to hemoglobin. Heme triggered rapid P selectin, C3aR, and C5aR expression and downregulated CD46 on endothelial cells. Importantly, complement deposition was attenuated in vivo and in vitro by heme scavenger hemopexin. In conclusion, we demonstrate that intravascular hemolysis triggers complement activation in vivo, encouraging further studies on its role in SCD nephropathy. Conversely, heme inhibition using hemopexin may provide a novel therapeutic opportunity to limit complement activation in hemolytic diseases.Lire moins >

Langue :

Anglais

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

Inserm
Université de Lille
CHU Lille

Collections :

• Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
• Lille Neurosciences & Cognition (LilNCog) - U 1172

Équipe(s) de recherche :

Glycation from inflammation to aging

Date de dépôt :

2019-03-01T14:08:06Z
2024-02-01T14:25:33Z