Matches in SemOpenAlex for { <https://semopenalex.org/work/W2587919917> ?p ?o ?g. }
Showing items 1 to 84 of
84
with 100 items per page.
- W2587919917 abstract "Abstract Hemolytic diseases, such as sickle cell anemia and thalassemia, are characterized by enhanced release of hemoglobin and heme into the circulation, heme-iron loading of reticulo-endothelial system macrophages as well as chronic inflammation. Here we demonstrate that in addition to activating the vascular endothelium, hemoglobin and heme alter the macrophage phenotype in sickle cell disease. We show that exposure of cultured macrophages to hemolytic aged red blood cells, heme or iron causes their functional phenotypic change towards a pro-inflammatory phenotype, with increased expression levels of inflammatory markers such as IL-6 (P<0.001), TNFα (P<0.0001), IL-1β (P<0.001) MHCII (P<0.001), CD86 (P<0.05) and CD14 (P<0.0001) and decreased expression levels of anti-inflammatory markers such as IL-10 (P<0.0001), CD206 (P<0.0001), Arginase-1 and Ym1. Interestingly, hemolysis and macrophage heme/iron accumulation in a mouse model of sickle cell disease triggers similar pro-inflammatory phenotypic alterations in hepatic macrophages, increasing the expression levels of IL-6 (P<0.0001), MHCII (P<0.05), CD86 (P<0.0001) and iNOS (P<0.01). On the mechanistic level, heme-induced pro-inflammatory phenotype switching of macrophages critically depends on ROS production and activation of the TLR4 signaling pathway. We further demonstrate that the heme scavenger hemopexin protects reticulo-endothelial macrophages from heme overload in heme-loaded Hx-null mice (P<0.05) and reduces production of cytokines (IL-6, TNFα: P<0.01) and reactive oxygen species (P<0.001). Importantly, in sickle mice the administration of human exogenous hemopexin attenuates the inflammatory phenotype of macrophages, by decreasing the expression of IL-6 (P<0.05), MHCII (P<0.01), CD86 (P<0.001) and iNOS (P<0.05). Taken together, our data suggest that therapeutical administration of hemopexin is beneficial to counteract heme-driven macrophage-mediated inflammation in sickle cell disease. Disclosures Brinkman: CSL Behring: Employment. Zuercher:CSL Behring: Employment." @default.
- W2587919917 created "2017-02-24" @default.
- W2587919917 creator A5001718937 @default.
- W2587919917 creator A5013757127 @default.
- W2587919917 creator A5032035671 @default.
- W2587919917 creator A5047794437 @default.
- W2587919917 creator A5053894320 @default.
- W2587919917 creator A5060970793 @default.
- W2587919917 creator A5064956979 @default.
- W2587919917 creator A5076434308 @default.
- W2587919917 creator A5078799080 @default.
- W2587919917 date "2015-12-03" @default.
- W2587919917 modified "2023-10-01" @default.
- W2587919917 title "The Heme Scavenger Hemopexin Reverts Heme-Driven Pro-Inflammatory Phenotypic Switching of Macrophages in Sickle Cell Disease" @default.
- W2587919917 doi "https://doi.org/10.1182/blood.v126.23.2205.2205" @default.
- W2587919917 hasPublicationYear "2015" @default.
- W2587919917 type Work @default.
- W2587919917 sameAs 2587919917 @default.
- W2587919917 citedByCount "0" @default.
- W2587919917 crossrefType "journal-article" @default.
- W2587919917 hasAuthorship W2587919917A5001718937 @default.
- W2587919917 hasAuthorship W2587919917A5013757127 @default.
- W2587919917 hasAuthorship W2587919917A5032035671 @default.
- W2587919917 hasAuthorship W2587919917A5047794437 @default.
- W2587919917 hasAuthorship W2587919917A5053894320 @default.
- W2587919917 hasAuthorship W2587919917A5060970793 @default.
- W2587919917 hasAuthorship W2587919917A5064956979 @default.
- W2587919917 hasAuthorship W2587919917A5076434308 @default.
- W2587919917 hasAuthorship W2587919917A5078799080 @default.
- W2587919917 hasConcept C1491633281 @default.
- W2587919917 hasConcept C181199279 @default.
- W2587919917 hasConcept C185592680 @default.
- W2587919917 hasConcept C202751555 @default.
- W2587919917 hasConcept C203014093 @default.
- W2587919917 hasConcept C2775858924 @default.
- W2587919917 hasConcept C2776217839 @default.
- W2587919917 hasConcept C2776474381 @default.
- W2587919917 hasConcept C2776914184 @default.
- W2587919917 hasConcept C2778620579 @default.
- W2587919917 hasConcept C2778917026 @default.
- W2587919917 hasConcept C2779244956 @default.
- W2587919917 hasConcept C55493867 @default.
- W2587919917 hasConcept C86803240 @default.
- W2587919917 hasConceptScore W2587919917C1491633281 @default.
- W2587919917 hasConceptScore W2587919917C181199279 @default.
- W2587919917 hasConceptScore W2587919917C185592680 @default.
- W2587919917 hasConceptScore W2587919917C202751555 @default.
- W2587919917 hasConceptScore W2587919917C203014093 @default.
- W2587919917 hasConceptScore W2587919917C2775858924 @default.
- W2587919917 hasConceptScore W2587919917C2776217839 @default.
- W2587919917 hasConceptScore W2587919917C2776474381 @default.
- W2587919917 hasConceptScore W2587919917C2776914184 @default.
- W2587919917 hasConceptScore W2587919917C2778620579 @default.
- W2587919917 hasConceptScore W2587919917C2778917026 @default.
- W2587919917 hasConceptScore W2587919917C2779244956 @default.
- W2587919917 hasConceptScore W2587919917C55493867 @default.
- W2587919917 hasConceptScore W2587919917C86803240 @default.
- W2587919917 hasLocation W25879199171 @default.
- W2587919917 hasOpenAccess W2587919917 @default.
- W2587919917 hasPrimaryLocation W25879199171 @default.
- W2587919917 hasRelatedWork W14338009 @default.
- W2587919917 hasRelatedWork W1543159336 @default.
- W2587919917 hasRelatedWork W1560154545 @default.
- W2587919917 hasRelatedWork W1970719589 @default.
- W2587919917 hasRelatedWork W2026278938 @default.
- W2587919917 hasRelatedWork W2036476586 @default.
- W2587919917 hasRelatedWork W2134633126 @default.
- W2587919917 hasRelatedWork W2408248598 @default.
- W2587919917 hasRelatedWork W2600218619 @default.
- W2587919917 hasRelatedWork W2607383608 @default.
- W2587919917 hasRelatedWork W2608296304 @default.
- W2587919917 hasRelatedWork W2805624241 @default.
- W2587919917 hasRelatedWork W2889671350 @default.
- W2587919917 hasRelatedWork W2890926420 @default.
- W2587919917 hasRelatedWork W2962116267 @default.
- W2587919917 hasRelatedWork W3016778010 @default.
- W2587919917 hasRelatedWork W3043727069 @default.
- W2587919917 hasRelatedWork W3127653521 @default.
- W2587919917 hasRelatedWork W3161729645 @default.
- W2587919917 hasRelatedWork W982599429 @default.
- W2587919917 isParatext "false" @default.
- W2587919917 isRetracted "false" @default.
- W2587919917 magId "2587919917" @default.
- W2587919917 workType "article" @default.