Oxidized hemoglobin forms contribute to NLRP3 inflammasome-driven IL-1β production upon intravascular hemolysis
| العنوان: | Oxidized hemoglobin forms contribute to NLRP3 inflammasome-driven IL-1β production upon intravascular hemolysis |
|---|---|
| المؤلفون: | Andrea Tóth, Mario D. Cordero, Judit Zsuzsa Erdei, Viktória Jeney, Béla Nagy, Enikő Balogh, György Paragh, Bernhard Ryffel, Benard Bogonko Nyakundi |
| المساهمون: | Enteric Bacterilogy and Foodborn Zoonoses, Institute of Experimental Medicine [Budapest] (KOKI), Hungarian Academy of Sciences (MTA)-Hungarian Academy of Sciences (MTA), Immunologie et Embryologie Moléculaires (IEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS) |
| المصدر: | Biochimica et Biophysica Acta-Molecular Basis of Disease Biochimica et Biophysica Acta-Molecular Basis of Disease, Elsevier, 2019, 1865 (2), pp.464-475. ⟨10.1016/j.bbadis.2018.10.030⟩ |
| بيانات النشر: | HAL CCSD, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, Inflammasomes, [SDV]Life Sciences [q-bio], Interleukin-1beta, Inflammation, Heme, Peritonitis, Hemolysis, 03 medical and health sciences, chemistry.chemical_compound, Hemoglobins, Mice, 0302 clinical medicine, NLR Family, Pyrin Domain-Containing 3 Protein, medicine, Extracellular, Macrophage, Animals, Elméleti orvostudományok, Molecular Biology, Methemoglobin, ComputingMilieux_MISCELLANEOUS, Innate immune system, Chemistry, Macrophages, Caspase 1, Pattern recognition receptor, Inflammasome, Orvostudományok, medicine.disease, 3. Good health, Cell biology, Enzyme Activation, Mice, Inbred C57BL, 030104 developmental biology, RAW 264.7 Cells, 030220 oncology & carcinogenesis, Molecular Medicine, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, medicine.symptom, Reactive Oxygen Species, Oxidation-Reduction, medicine.drug |
| الوصف: | Damage 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, both hemolysis-induced and FHb-induced pro-inflammatory responses were largely attenuated in Nlrp3-/- mice. Taken together, FHb is a potent trigger of NLRP3 activation and production of IL-1β in vitro and in vivo, suggesting that FHb may contribute to hemolysis-induced inflammation. Identification of RBC-derived DAMPs might allow us to develop new therapeutic approaches for hemolytic diseases. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 0925-4439 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::20eb8d2806b329088d438b0c78243c1bTest https://hal-cnrs.archives-ouvertes.fr/hal-02126382Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....20eb8d2806b329088d438b0c78243c1b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 09254439 |
|---|