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International Journal of Inflammation
Volume 2013 (2013), Article ID 980327, 7 pages
Research Article

Haptoglobin Genotype-Dependent Anti-Inflammatory Signaling in CD163+ Macrophages

1Edmund Cohen Laboratory for Vascular Research, Chronic Disease Research Centre, The University of the West Indies Bridgetown BB11115, Barbados
2Eric Bywaters Centre for Vascular Inflammation, Faculty of Medicine, Imperial College London, London W12 0NN, UK
3Department of Life Sciences, University of Bedfordshire, Luton LU1 3JU, UK

Received 15 March 2013; Accepted 3 April 2013

Academic Editor: David A. Hart

Copyright © 2013 R. Clive Landis et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Intraplaque hemorrhage causes adaptive remodelling of macrophages towards a protective phenotype specialized towards handling iron and lipid overload, denoted Mhem. The Mhem phenotype expresses elevated levels of hemoglobin (Hb) scavenger receptor, CD163, capable of endocytosing pro-oxidant free Hb complexed to acute phase protein haptoglobin (Hp). It is notable that individuals homozygous for the Hp 2 allele (a poorer antioxidant) are at increased risk of cardiovascular disease compared to the Hp 1 allele. In this study, we examined whether scavenging of polymorphic Hp:Hb complexes differentially generated downstream anti-inflammatory signals in cultured human macrophages culminating in interleukin (IL)-10 secretion. We describe an anti-inflammatory signalling pathway involving phosphatidylinositol-3-kinase activation upstream of Akt phosphorylation (pSer473Akt) and IL-10 secretion. The pathway is mediated specifically through CD163 and is blocked by anti-CD163 antibody or phagocytosis inhibitor. However, levels of pSer473Akt and IL-10 were significantly diminished when scavenging polymorphic Hp2-2:Hb complexes compared to Hp1-1:Hb complexes . Impaired anti-inflammatory macrophage signaling through a CD163/pAkt/IL-10 axis may thus represent a possible Hp2-2 disease mechanism in atherosclerosis.