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Landis RC, Philippidis P, Domin J, et al. Haptoglobin Genotype-Dependent Anti-Inflammatory Signaling in CD163(+) Macrophages. Int J Inflam. 2013;2013:980327doi: 10.1155/2013/980327.
Landis, R. C., Philippidis, P., Domin, J., Boyle, J. J., & Haskard, D. O. (2013). Haptoglobin Genotype-Dependent Anti-Inflammatory Signaling in CD163(+) Macrophages. International journal of inflammation, 2013980327. https://doi.org/10.1155/2013/980327
Landis, R Clive, et al. "Haptoglobin Genotype-Dependent Anti-Inflammatory Signaling in CD163(+) Macrophages." International journal of inflammation vol. 2013 (2013): 980327. doi: https://doi.org/10.1155/2013/980327
Landis RC, Philippidis P, Domin J, Boyle JJ, Haskard DO. Haptoglobin Genotype-Dependent Anti-Inflammatory Signaling in CD163(+) Macrophages. Int J Inflam. 2013;2013:980327. doi: 10.1155/2013/980327. Epub 2013 Apr 23. PMID: 23710416; PMCID: PMC3655560.
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Int J Inflam. 2013;2013:980327. doi: 10.1155/2013/980327. Epub 2013 Apr 23.

Haptoglobin Genotype-Dependent Anti-Inflammatory Signaling in CD163(+) Macrophages.

International journal of inflammation

R Clive Landis, Pandelis Philippidis, Jan Domin, Joseph J Boyle, Dorian O Haskard

Affiliations

  1. Edmund Cohen Laboratory for Vascular Research, Chronic Disease Research Centre, The University of the West Indies Bridgetown BB11115, Barbados ; Eric Bywaters Centre for Vascular Inflammation, Faculty of Medicine, Imperial College London, London W12 0NN, UK.

PMID: 23710416 PMCID: PMC3655560 DOI: 10.1155/2013/980327

Abstract

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 (P < 0.05). Impaired anti-inflammatory macrophage signaling through a CD163/pAkt/IL-10 axis may thus represent a possible Hp2-2 disease mechanism in atherosclerosis.

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