The haptoglobin-CD163-heme oxygenase-1 pathway for hemoglobin scavenging

Oxid Med Cell Longev. 2013;2013:523652. doi: 10.1155/2013/523652. Epub 2013 May 27.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antigens, CD / metabolism*
  • Antigens, Differentiation, Myelomonocytic / metabolism*
  • Haptoglobins / chemistry
  • Haptoglobins / metabolism*
  • Heme / metabolism
  • Heme Oxygenase-1 / metabolism*
  • Hemoglobins / metabolism*
  • Humans
  • Protein Binding
  • Receptors, Cell Surface / metabolism*

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD163 antigen
  • Haptoglobins
  • Hemoglobins
  • Receptors, Cell Surface
  • Heme
  • Heme Oxygenase-1