Haptoglobin Genotype-Dependent Anti-Inflammatory Signaling in CD163+ Macrophages
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...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2013-01-01
|
| Series: | International Journal of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2013/980327 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832548901255643136 |
|---|---|
| author | R. Clive Landis Pandelis Philippidis Jan Domin Joseph J. Boyle Dorian O. Haskard |
| author_facet | R. Clive Landis Pandelis Philippidis Jan Domin Joseph J. Boyle Dorian O. Haskard |
| author_sort | R. Clive Landis |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-8bfc4e5378fd48da979cadc63c883071 |
| institution | Kabale University |
| issn | 2090-8040 2042-0099 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Inflammation |
| spelling | doaj-art-8bfc4e5378fd48da979cadc63c8830712025-02-03T06:12:46ZengWileyInternational Journal of Inflammation2090-80402042-00992013-01-01201310.1155/2013/980327980327Haptoglobin Genotype-Dependent Anti-Inflammatory Signaling in CD163+ MacrophagesR. Clive Landis0Pandelis Philippidis1Jan Domin2Joseph J. Boyle3Dorian O. Haskard4Edmund Cohen Laboratory for Vascular Research, Chronic Disease Research Centre, The University of the West Indies Bridgetown BB11115, BarbadosEric Bywaters Centre for Vascular Inflammation, Faculty of Medicine, Imperial College London, London W12 0NN, UKDepartment of Life Sciences, University of Bedfordshire, Luton LU1 3JU, UKEric Bywaters Centre for Vascular Inflammation, Faculty of Medicine, Imperial College London, London W12 0NN, UKEric Bywaters Centre for Vascular Inflammation, Faculty of Medicine, Imperial College London, London W12 0NN, UKIntraplaque 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.http://dx.doi.org/10.1155/2013/980327 |
| spellingShingle | R. Clive Landis Pandelis Philippidis Jan Domin Joseph J. Boyle Dorian O. Haskard Haptoglobin Genotype-Dependent Anti-Inflammatory Signaling in CD163+ Macrophages International Journal of Inflammation |
| title | Haptoglobin Genotype-Dependent Anti-Inflammatory Signaling in CD163+ Macrophages |
| title_full | Haptoglobin Genotype-Dependent Anti-Inflammatory Signaling in CD163+ Macrophages |
| title_fullStr | Haptoglobin Genotype-Dependent Anti-Inflammatory Signaling in CD163+ Macrophages |
| title_full_unstemmed | Haptoglobin Genotype-Dependent Anti-Inflammatory Signaling in CD163+ Macrophages |
| title_short | Haptoglobin Genotype-Dependent Anti-Inflammatory Signaling in CD163+ Macrophages |
| title_sort | haptoglobin genotype dependent anti inflammatory signaling in cd163 macrophages |
| url | http://dx.doi.org/10.1155/2013/980327 |
| work_keys_str_mv | AT rclivelandis haptoglobingenotypedependentantiinflammatorysignalingincd163macrophages AT pandelisphilippidis haptoglobingenotypedependentantiinflammatorysignalingincd163macrophages AT jandomin haptoglobingenotypedependentantiinflammatorysignalingincd163macrophages AT josephjboyle haptoglobingenotypedependentantiinflammatorysignalingincd163macrophages AT dorianohaskard haptoglobingenotypedependentantiinflammatorysignalingincd163macrophages |