Induction of NLRP3 Inflammasome Activation by Heme in Human Endothelial Cells. (20th March 2018)

• Record Type: Journal Article
• Authors: Erdei, Judit; Tóth, Andrea; Balogh, Enikő; Nyakundi, Benard Bogonko; Bányai, Emese; Ryffel, Bernhard; Paragh, György; Cordero, Mario D.; Jeney, Viktória
• Other Names: Mittal Manish Academic Editor.
• Is Part Of: Oxidative medicine and cellular longevity. Volume 2018(2018)
• Publication Date: 2018-03-20
• Subjects: Oxidative stress -- Periodicals; Cells -- Aging -- Periodicals; Cells -- Aging; Oxidative stress; Oxidative Stress -- Periodicals; Cell Aging -- Periodicals; Periodicals; 611.0181
• DOI: 10.1155/2018/4310816
• Languages: English
• ISSNs: 1942-0900

Abstract

Abstract : Hemolytic or hemorrhagic episodes are often associated with inflammation even when infectious agents are absent suggesting that red blood cells (RBCs) release damage-associated molecular patterns (DAMPs). DAMPs activate immune and nonimmune cells through pattern recognition receptors. Heme, released from RBCs, is a DAMP and induces IL-1 β production through the activation of the nucleotide-binding domain and leucine-rich repeat-containing family and pyrin domain containing 3 (NLRP3) in macrophages; however, other cellular targets of heme-mediated inflammasome activation were not investigated. Because of their location, endothelial cells can be largely exposed to RBC-derived DAMPs; therefore, we investigated whether heme and other hemoglobin- (Hb-) derived species induce NLRP3 inflammasome activation in these cells. We found that heme upregulated NLRP3 expression and induced active IL-1 β production in human umbilical vein endothelial cells (HUVECs). LPS priming largely amplified the heme-mediated production of IL-1 β . Heme administration into C57BL/6 mice induced caspase-1 activation and cleavage of IL-1 β which was not observed in NLRP3 −/− mice. Unfettered production of reactive oxygen species played a critical role in heme-mediated NLRP3 activation. Activation of NLRP3 by heme required structural integrity of the heme molecule, as neither protoporphyrin IX nor iron-induced IL-1 β production. Neither naive nor oxidized forms of Hb were able to induce IL-1 β production in HUVECs. Our results identified endothelial cells as a target of heme-mediated NLRP3 activation that can contribute to the inflammation triggered by sterile hemolysis. Thus, understanding the characteristics and cellular counterparts of RBC-derived DAMPs might allow us to identify new therapeutic targets for hemolytic diseases.