Oxidized hemoglobin forms contribute to NLRP3 inflammasome-driven IL-1β production upon intravascular hemolysis

Publication date: Available online 30 October 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Benard Bogonko Nyakundi, Andrea Tóth, Enikő Balogh, Béla Nagy, Judit Erdei, Bernhard Ryffel, György Paragh, Mario D. Cordero, Viktória JeneyAbstractDamage associated molecular patterns (DAMPs) are released form red blood cells (RBCs) during intravascular hemolysis (IVH). Extracellular heme, with its pro-oxidant, pro-inflammatory and cytotoxic effects, is sensed by innate immune cells through pattern recognition receptors such as toll-like receptor 4 and nucleotide-binding domain and leucine rich repeat containing family, pyrin domain containing 3 (NLRP3), while free availability of heme is strictly controlled. Here we investigated the involvement of different hemoglobin (Hb) forms in hemolysis-associated inflammatory responses.We found that after IVH most of the extracellular heme molecules are localized in oxidized Hb forms. IVH was associated with caspase-1 activation and formation of mature IL-1β in plasma and in the liver of C57BL/6 mice. We showed that ferrylHb (FHb) induces active IL-1β production in LPS-primed macrophages in vitro and triggered intraperitoneal recruitment of neutrophils and monocytes, caspase-1 activation and active IL-1β formation in the liver of C57BL/6 mice. NLRP3 deficiency provided a survival advantage upon IVH, without influencing the extent of RBC lysis or the accumulation of oxidized Hb forms. However, bot...

Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 30, 2018 Category: Molecular Biology Source Type: research