Title :

Characterization of Renal Injury and Inflammation in an Experimental Model of Intravascular Hemolysis

Author(s) :

Merle Nicolas, S [Auteur]
Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)]
Grunenwald, Anne [Auteur]
Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)]
Figueres, Marie-Lucile [Auteur]
Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)]
Chauvet, Sophie [Auteur]
Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)]
Daugan, Marie [Auteur]
Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)]
Knockaert, Samantha [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)]
Noe, Remi [Auteur]
Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)]
May, Olivia [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)]
Frimat, Marie [Auteur]
Lille Inflammation Research International Center (LIRIC) - U995
Brinkman, Nathan [Auteur]
Gentinetta, Thomas [Auteur]
Miescher, Sylvia [Auteur]
Houillier, Pascal [Auteur]
Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)]
Legros, Veronique [Auteur]
Université Paris-Saclay
Gonnet, Florence [Auteur]
Université Paris-Saclay
Blanc-Brude Olivier, P [Auteur]
Université Paris Descartes - Paris 5 [UPD5]
Rabant, Marion [Auteur]
Daniel, Regis [Auteur]
Université Paris-Saclay
Dimitrov Jordan, D [Auteur]
Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)]
Roumenina Lubka, T [Auteur]
Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)]

Journal title :

Frontiers in Immunology

Abbreviated title :

Front. Immunol.

Volume number :

9

Publication date :

2018-03-01

ISSN :

1664-3224

Keyword(s) :

inflammation
endothelial activation
kidney injury
heme
hemolysis
experimental model of intravascular hemolysis
hemopexin
phenylhydrazine

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Intravascular erythrocyte destruction, accompanied by the release of pro-oxidative and pro-inflammatory components hemoglobin and heme, is a common event in the pathogenesis of numerous diseases with heterogeneous etiology ...
Show more >Intravascular erythrocyte destruction, accompanied by the release of pro-oxidative and pro-inflammatory components hemoglobin and heme, is a common event in the pathogenesis of numerous diseases with heterogeneous etiology and clinical features. A frequent adverse effect related to massive hemolysis is the renal injury and inflammation. Nevertheless, it is still unclear whether heme––a danger-associated molecular pattern––and ligand for TLR4 or upstream hemolysis-derived products are responsible for these effects. Well-characterized animal models of hemolysis with kidney impairment are needed to investigate how hemolysis drives kidney injury and to test novel therapeutic strategies. Here, we characterized the pathological processes leading to acute kidney injury and inflammation during massive intravascular hemolysis, using a mouse model of phenylhydrazine (PHZ)-triggered erythrocyte destruction. We observed profound changes in mRNA levels for markers of tubular damage (Kim-1, NGAL) and regeneration (indirect marker of tubular injury, Ki-67), and tissue and vascular inflammation (IL-6, E-selectin, P-selectin, ICAM-1) in kidneys of PHZ-treated mice, associated with ultrastructural signs of tubular injury. Moreover, mass spectrometry revealed presence of markers of tubular damage in urine, including meprin-α, cytoskeletal keratins, α-1-antitrypsin, and α-1-microglobulin. Signs of renal injury and inflammation rapidly resolved and the renal function was preserved, despite major changes in metabolic parameters of PHZ-injected animals. Mechanistically, renal alterations were largely heme-independent, since injection of free heme could not reproduce them, and scavenging heme with hemopexin in PHZ-administered mice could not prevent them. Reduced overall health status of the mice suggested multiorgan involvement. We detected amylasemia and amylasuria, two markers of acute pancreatitis. We also provide detailed characterization of renal manifestations associated with acute intravascular hemolysis, which may be mediated by hemolysis-derived products upstream of heme release. This analysis provides a platform for further investigations of hemolytic diseases and associated renal injury and the evaluation of novel therapeutic strategies that target intravascular hemolysis.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Inserm
Université de Lille
CHU Lille

Collections :

• Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286

Research team(s) :

Glycation from inflammation to aging

Submission date :

2019-03-01T14:35:40Z
2024-03-04T10:18:03Z