title: The haptoglobin-CD163-heme oxygenase-1 pathway for hemoglobin scavenging.
abstract: The haptoglobin- (Hp-) CD163-heme oxygenase-1 (HO-1) pathway is an efficient captor-receptor-enzyme system to circumvent the hemoglobin (Hb)/heme-induced toxicity during physiological and pathological hemolyses. In this pathway, Hb tightly binds to Hp leading to CD163-mediated uptake of the complex in macrophages followed by lysosomal Hp-Hb breakdown and HO-1-catalyzed conversion of heme into the metabolites carbon monoxide (CO), biliverdin, and iron. The plasma concentration of Hp is a limiting factor as evident during accelerated hemolysis, where the Hp depletion may cause serious Hb-induced toxicity and put pressure on backup protecting systems such as the hemopexin-CD91-HO pathway. The Hp-CD163-HO-1 pathway proteins are regulated by the acute phase mediator interleukin-6 (IL-6), but other regulatory factors indicate that this upregulation is a counteracting anti-inflammatory response during inflammation. The heme metabolites including bilirubin converted from biliverdin have overall an anti-inflammatory effect and thus reinforce the anti-inflammatory efficacy of the Hp-CD163-HO-1 pathway. Future studies of animal models of inflammation should further define the importance of the pathway in the anti-inflammatory response.
authors.affiliation: Department of Biomedicine, University of Aarhus, Aarhus C, Denmark.
authors.forename: Jens Haugbølle
authors.initials: JH
authors.lastname: Thomsen
authors.forename: Anders
authors.initials: A
authors.lastname: Etzerodt
authors.forename: Pia
authors.initials: P
authors.lastname: Svendsen
authors.forename: Søren K
authors.initials: SK
authors.lastname: Moestrup
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism*; D006242:Haptoglobins / Q000737:chemistry / Q000378:metabolism*; D006418:Heme / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000378:metabolism*; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D006242:Haptoglobins; D006454:Hemoglobins; D011956:Receptors, Cell Surface; D006418:Heme; D051547:Heme Oxygenase-1