Imperial College London
Alternate

Dr Joseph J Boyle

Faculty of Medicine, National Heart & Lung Institute

Clinical Reader in Vascular Molecular Pathology
 
 
 
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Contact

 

+44 (0)20 7594 2723joseph.boyle Website

 
 
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Location

 

L536ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Landis:2013:2013/980327,
author = {Landis, RC and Philippidis, P and Domin, J and Boyle, JJ and Haskard, DO},
doi = {2013/980327},
journal = {International Journal of Inflammation},
title = {Haptoglobin Genotype-Dependent Anti-Inflammatory Signaling in CD163(+) Macrophages.},
url = {http://dx.doi.org/10.1155/2013/980327},
volume = {2013},
year = {2013}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - Landis,RC
AU  - Philippidis,P
AU  - Domin,J
AU  - Boyle,JJ
AU  - Haskard,DO
DO  - 2013/980327
PY  - 2013///
SN  - 2042-0099
TI  - Haptoglobin Genotype-Dependent Anti-Inflammatory Signaling in CD163(+) Macrophages.
T2  - International Journal of Inflammation
UR  - http://dx.doi.org/10.1155/2013/980327
UR  - http://hdl.handle.net/10044/1/51899
VL  - 2013
ER  -
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