Title: Atherosclerotic intralesional haemorrhage moulds monocyte differentiation into a macrophage antioxidant phenotype bearing the hemoglobin scavenger receptor CD163
Abstract: Atherosclerotic intralesional haemorrhage promotes plaque progression. We investigated macrophage differentiation in atherosclerotic plaques with intralesional hemorrhage and in vitro with hemoglobin:haptoglobin (Hb:Hp) complexes. Macrophages within culprit lesions partitioned into reciprocal populations, with 26.1±2.3% expressing high levels of CD163 but depressed HLA‐DR (CD163 high ‐HLA‐DR low phenotype), and the remainder 72.5±2.4% expressing the inverse (classical inflammatory) phenotype (CD163 low ‐HLA‐DR high ). CD163 high macrophages were associated with areas of hemorrhage (P<0.008), expressed increased (antioxidant) heme oxygenase‐1 (P<0.00001), and were protected from oxidant stress (P<0.003), despite greater iron content (P<0.001). This phenotype was reproduced in vitro by differentiating human monocytes with Hb:Hp, which required phagocytosis of Hb:Hp via CD163 and was inhibited by anti‐IL‐10. The divergent commitment of macrophages to CD163 high or CD163 low phenotypes was predictively modelled using a systems biology approach incorporating an IL‐10 autocrine positive feedback loop. Our results provide evidence for a novel CD163 high macrophage subset within culprit lesions. This appears to be moulded by the local microenvironment to become ‘fit for purpose’ for clearing Hb. Its therapeutic induction may reduce plaque progression. Funded by the British Heart Foundation
Publication Year: 2008
Publication Date: 2008-03-01
Language: en
Type: article
Indexed In: ['crossref']
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