Divergent roles of haptoglobin and hemopexin deficiency for disease progression of Shiga-toxin–induced hemolytic-uremic syndrome in mice

Abstract

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Iron Metabolism and Immune Regulation

“…In some iron-overload disease, iron promotes neutrophils recruitment and inflammation by upregulating IL-1β ( 36 ). In Shiga-toxin-induced hemolytic–uremic syndrome, heme-scavenging proteins, haptoglobin, attenuated kidney platelet deposition and neutrophil recruitment, revealing the potential correlation between iron and neutrophil recruitment ( 37 ).…”

Bruton’s tyrosine kinase inhibition attenuates disease progression by reducing renal immune cell invasion in mice with hemolytic-uremic syndrome

“…Thereby, the secretion of interleukin-8 or monocyte chemotactic protein 1 of the Stx-affected cells generates an inflammatory environment, while simultaneously enhancing immune cell adhesion and their migration into renal tissue (33-35). Therefore, it is not surprising that recruitment of macrophages, neutrophils and other immune cells is well documented in murine kidneys of our HUS model as well as in HUS patients (18,19,36). Interestingly, binding of Stx to neutrophils prolongs their lifespan, increases reactive oxygen species production and neutrophil extracellular trap formation and thereby intensifying the inflammatory process, indicating neutrophils are an important player in HUS pathophysiology (37).…”

“…Body weight was monitored daily and disease progression was evaluated three times daily using an established HUS score (Supplementary Table S1), in which the disease severity was categorized from 1 = no signs of illness to 5 = dead. Survival was monitored up to day 7 using humane endpoints (18,19). Animals were exsanguinated in deep anesthesia (100 mg/kg ketamine; 10 mg/kg xylazine) and perfused with 0.9% NaCl.…”

Double-edged functions of hemopexin in hematological related diseases: from basic mechanisms to clinical application

“…While HPX deficiency promotes AKI in sickle cell mice under hemolytic stress, HPX injection did not alter hemoglobinuria (24, 25). In a Shigatoxin-induced HUS mouse model, HPX knockout mice displayed improved survival and reduced tubular iron deposition compared to wild-type mice (67).…”

“…However, HPX does not always act as a protective factor in infection-related hemolysis. For instance, in a mouse model of Shiga toxin-induced hemolytic-uremic syndrome (HUS), HPX deficiency was protective in resolving HUS pathology (67). HPX -/mice exhibited higher survival rates when challenged with Shiga toxin, with reduced renal inflammation characterized by decreased macrophage and neutrophil recruitment and C3c deposition [66].…”