Impaired Immunosuppressive Effect of Bronchoalveolar Mesenchymal Stem Cells in Hypersensitivity Pneumonitis: preliminary findings

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Ferryl Hemoglobin Inhibits Osteoclastic Differentiation of Macrophages in Hemorrhaged Atherosclerotic Plaques

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Hydrogen Sulfide Abrogates Hemoglobin-Lipid Interaction In Atherosclerotic Lesion

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Hydrogen Sulfide Abrogates Hemoglobin-Lipid Interaction in Atherosclerotic Lesion

This is the final version of the article. Available from Hindawi Publishing Corporation via the DOI in this record.The infiltration of red blood cells into atheromatous plaques is implicated in atherogenesis. Inside the lesion, hemoglobin (Hb) is oxidized to ferri-and ferrylHb which exhibit prooxidant and proinflammatory activities. Cystathione gamma-lyase-(CSE-) derived H 2 S has been suggested to possess various antiatherogenic actions. Expression of CSE was upregulated predominantly in macrophages, foam cells, and myofibroblasts of human atherosclerotic lesions derived from carotid artery specimens of patients. A similar pattern was observed in aortic lesions of apolipoprotein E-deficient mice on high-fat diet. We identified several triggers for inducing CSE expression in macrophages and vascular smooth muscle cells including heme, ferrylHb, plaque lipids, oxidized low-density lipoprotein, tumor necrosis factor-α, and interleukin-1β. In the interplay between hemoglobin and atheroma lipids, H 2 S significantly mitigated oxidation of Hb preventing the formation of ferrylHb derivatives, therefore providing a novel function as a heme-redox-intermediate-scavenging antioxidant. By inhibiting Hb-lipid interactions, sulfide lowered oxidized Hb-mediated induction of adhesion molecules in endothelium and disruption of endothelial integrity. Exogenous H 2 S inhibited heme and Hb-mediated lipid oxidation of human atheroma-derived lipid and human complicated lesion. Our study suggests that the CSE/H 2 S system represents an atheroprotective pathway for removing or limiting the formation of oxidized Hb and lipid derivatives in the atherosclerotic plaque.The research group is supported by the Hungarian Academy of Sciences (11003). This work was supported by Hungarian Government Grants (OTKA) K112333 (József Balla), K109843 (Péter Nagy), and K116024 (Viktória Jeney) and Marie Curie International Reintegration Grant PIRG08-GA-2010-277006 (Péter Nagy). Péter Nagy is a János Bolyai Research Scholar of the Hungarian Academy of Sciences. Viktória Jeney was supported by Zoltán Magyary Fellowship (TÁMOP 4.2.4.A/2-11/1-2012-0001). László Potor was supported by János Apáczai-Csere Fellowship (TÁMOP 4.2.4.A/2-11/1-2012-0001). The project was cofinanced by the European Union and the European Social Fund (ESF) GINOP-2.3.2-15-2016-00043 IRONHEARTH and EFOP-3.6.2-16-2017-00006 LIVE LONGER