Article
Heme triggers TLR4 signaling leading to endothelial cell activation and vaso-occlusion in murine sickle cell disease.
Blood - 16 Jan 2014
Belcher John D, Chen Chunsheng, Nguyen Julia, Milbauer Liming, Abdulla Fuad, Alayash Abdu I, Smith Ann, Nath Karl A, Hebbel Robert P, Vercellotti Gregory M
Abstract excerpt
Treatment of sickle cell disease (SCD) is hampered by incomplete understanding of pathways linking hemolysis to vaso-occlusion. We investigated these pathways in transgenic sickle mice. Infusion of hemoglobin or heme triggered vaso-occlusion in sickle, but not normal, mice. Methemoglobin, but not heme-stabilized cyanomethemoglobin, induced vaso-occlusion, indicating heme liberation is necessary. In corroboration,...
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