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001-es BibID:	BIBFORM078435
035-os BibID:	(PMID)30389578
Első szerző:	Nyakundi, Benard Bogonko (biokémikus)
Cím:	Oxidized hemoglobin forms contribute to NLRP3 inflammasome-driven IL1[beta] production upon intravascular hemolysis / Benard Bogonko Nyakundi, Andrea Tóth, Enikő Balogh, Béla Nagy, Judit Erdei, Bernhard Ryffel, György Paragh, Mario D. Cordero, Viktória Jeney
Dátum:	2019
Megjegyzések:	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.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban Ferryl hemoglobin Heme Hemolysis IL-1β Macrophage NLRP3 inflammasome activation
Megjelenés:	Biochimica et biophysica acta. Molecular basis of disease. - 1865 : 2 (2019), p. 464-475. -
További szerzők:	Tóth Andrea (1992-) (molekuláris biológus) Balogh Enikő (1987-) (molekuláris biológus) Nagy Béla Jr. (1980-) (labordiagnosztikai szakorvos) Erdei Judit Zsuzsa (1992-) (vegyész) Ryffel, Bernhard Paragh György (1953-) (belgyógyász) Cordero, Mario D. Jeney Viktória (1971-) (vegyész, kémia tanár)
Pályázati támogatás:	NKFIH K116024 NKFIH GINOP-2.3.2-15-2016-00005 GINOP
Internet cím:	Intézményi repozitóriumban (DEA) tárolt változat DOI
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