Hemoglobin Scavenger Receptor CD163 Mediates Interleukin-10 Release and Heme Oxygenase-1 Synthesis: Antiinflammatory Monocyte-Macrophage Responses In Vitro, in Resolving Skin Blisters In Vivo, and After Cardiopulmonary Bypass Surgery
Abstract
The recently described hemoglobin scavenger receptor CD163 mediates the endocytosis of hemoglobin:haptoglobin (Hb:Hp) complexes and thereby counters Hb-induced oxidative tissue damage after hemolysis. Although CD163 has been indirectly associated with antiinflammatory and atheroprotective activity, no ligand-receptor-effector pathway has yet been described for this receptor. To understand the significance of CD163 and more clearly define downstream pathways linked to inflammatory resolution, we studied the expression and function of CD163 in human monocytes/macrophages using both in vitro and in vivo models. Differentiation of human blood monocytes into macrophages either by in vitro culture or in resolving cantharidin-induced skin blisters led to an equivalent increase (>15×) in CD163 expression. Elevated CD163 levels were also noted on circulating monocytes in cardiac surgical patients during the resolution phase of the systemic inflammatory response to cardiopulmonary bypass surgery. In each case, binding of Hb:Hp to CD163-bearing cells elicited potent interleukin-10 secretion, and this was inhibited by the anti-CD163 antibody RM3/1. Release of interleukin-10, in turn, induced heme oxygenase-1 stress protein synthesis via an autocrine mechanism. Such induction of heme oxygenase-1 was observed in vivo 24 to 48 hours after the onset of cardiopulmonary bypass surgery. These results identify novel antiinflammatory and cytoprotective effector pathways in human monocytes/macrophages related to Hb scavenging and metabolism, which may have relevance in atheroprotection, wound healing, and patient recovery postoperatively.
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ITGAV displayed strong co-expression with CD163.
“In the same spectrum, integrin alpha V (ITGAV) displayed strong co-expression with CD163, a well known macrophage-specific marker mediating an anti-inflammatory pathway that includes IL10, and whose synthesis was shown to be well correlated with local and systemic inflammatory phenomena [37,38].”
From Adipose tissue transcriptomic signature highlights the pathological relevance of extracellular matrix in human obesity (2008) · cites this paper as [38]
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- Authors
- Philippidis, P., Mason, J. C., Evans, B. J., Nadra, I., Taylor, K. M., Haskard, D. O., & Landis, R. C.
- Affiliations
- Hammersmith Hospital (GB)
- Venue
- Circulation Research
- Published
- 2004-01-09
- Volume
- 94
- Issue
- 1
- Pages
- 119-126
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- OpenAlex
- W2143009142
- Cited by
- 476
- References
- 43
- Citations by year
- 2026: 16 · 2025: 12 · 2024: 7 · 2023: 15 · 2022: 20 · 2021: 18 · 2020: 25 · 2019: 23 · 2018: 18 · 2017: 27 · 2016: 17 · 2015: 34 · 2014: 20 · 2013: 26 · 2012: 31
- FWCI
- 6.55
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- British Heart Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heme Oxygenase-1 and Carbon Monoxide
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Keywords
- CD163, haptoglobin, hemoglobin-haptoglobin complex, IL-10, heme oxygenase-1, monocytes, macrophages, inflammation resolution, cardiopulmonary bypass, hemolysis, anti-inflammatory pathways, atheroprotection, wound healing
- MeSH terms
- CD163 Antigen, Aged, Coronary Artery Bypass, Blister, Cardiopulmonary Bypass, Cells, Cultured, Female, Haptoglobins, Heme Oxygenase (Decyclizing), Hemoglobins, Humans, Inflammation, Macrophages, Male, Membrane Proteins, Middle Aged, Monocytes, Receptors, Cell Surface, Antigens, Differentiation, Myelomonocytic, Antigens, CD, Interleukin-10, Autocrine Communication, Heme Oxygenase-1
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