Disease relevance of CD163

• OBJECTIVE: Since CD163+ macrophages are selectively increased in spondylarthropathy (SpA) synovitis, we investigated the role of CD163+ macrophages in synovial inflammation [1].
• The haptoglobin-dependent HbSR/CD163 scavenging system for hemoglobin clearance prevents toxic effects of hemoglobin in plasma and kidney and explains the decrease in the haptoglobin plasma concentration in patients with accelerated hemolysis [2].
• The HbSR/CD163 activity may be of quantitative importance for iron uptake in macrophages in general and for some iron-associated pathological processes, e.g. the atherogenesis-promoting oxidation of LDL leading to foam cell formation and apoptosis in the vessel wall [2].
• CD163 identifies a unique population of ramified microglia in HIV encephalitis (HIVE) [3].
• Finally, we demonstrate a marked increase in surface CD163 expression on circulating monocytes 24 h following experimental endotoxemia [4].
• In chronically infected animals with encephalitis, CD163 expression was detected in activated microglia surrounding SIV encephalitis lesions in the presence of Hp-Hb complex, suggesting leakage of the blood-brain barrier [5].

Psychiatry related information on CD163

• The activation state identified by CD163 has not been previously recognized and may have a positive or negative impact on neuronal damage shown in HIV-associated dementia [3].
• This study investigated the expression of CD 163, a cell surface marker whose normal expression is restricted to monocytes/macrophages, in cases of HIV or SIV encephalitis (HIVE/SIVE), Alzheimer disease, and variant Creutzfeldt-Jakob disease [3].

High impact information on CD163

• Complexes of haemoglobin and multimeric haptoglobin (the 2-2 phenotype) exhibit higher functional affinity for CD 163 than do complexes of haemoglobin and dimeric haptoglobin (the 1-1 phenotype) [6].
• CD163 mediates the internalization of hemoglobin-haptoglobin (Hb-Hp) complexes by macrophages [7].
• Not only is Hb internalized into an endosomal compartment by CD163 as a result of active receptor-dependent endocytosis; it also inhibits the uptake of Hb-Hp complexes, suggesting a common receptor-binding site [7].
• Free Hb further induces heme oxygenase mRNA expression in CD163+ HEK293 cells, but not in CD163- cells [7].
• However, in contrast to Hp, Hpr did not promote any high-affinity binding to the scavenger receptor CD163 [8].

Chemical compound and disease context of CD163

• As hemoglobin can bind LPS and enhance its toxicity, it will be important to determine how cell surface and soluble CD163 influence inflammatory processes during sepsis [4].
• The hemoglobin scavenger receptor (HbSR) CD163 is a monocyte/macrophage-specific glycoprotein that binds and facilitates uptake of haptoglobin-hemoglobin (Hp-Hb) complexes, which are rapidly formed in the circulation upon hemolysis of red blood cells [9].
• Because opioid peptides might be of importance in inflammatory skin diseases, for example psoriasis, sections of skin from psoriatic patients were immunohistochemically stained with antisera against methionine and leucine enkephalin, CD68 (KP1, PG-M1), calprotectin (M747), M130 (Ber-MAC3), CD1a and CD3 [10].

Biological context of CD163

• The mAb 2A10 recognizes a 120-kDa protein with sequence homology to the human CD163 and whose expression is restricted to the cells of the porcine monocyte/macrophage lineage [11].
• Hemoglobin in plasma is instantly bound with high affinity to haptoglobin--an interaction leading to the recognition of the complex by HbSR/CD163 and endocytosis in macrophages [2].
• The existence of several CD163 isoforms, which differ in the structure of their cytoplasmic domains and putative phosphorylation sites, suggests that these isoforms also differ in their signaling mechanism [12].
• Endotoxin induces rapid metalloproteinase-mediated shedding followed by up-regulation of the monocyte hemoglobin scavenger receptor CD163 [4].
• Cross-linking of CD163 on glucocorticoid-stimulated macrophages results in the secretion of several proinflammatory cytokines, but the precise mechanism of CD163 mediated signal transduction is not understood [12].

Anatomical context of CD163

• Local production of sCD163 was evidenced by a 5-7-fold higher level of sCD163 in SF than in serum and by the correlation with synovial lining CD163+ macrophages in SpA [1].
• All brightly CD14+ cells in or around vessel walls (interpreted as immigrant monocytes) were CD163+ [13].
• RESULTS: CD163 was observed on all CD14+ cells in synovium and tonsil with the exception of cells within larger T lymphocyte clusters in synovium and within tonsillar follicles [13].
• Macrophage subpopulations in rheumatoid synovium: reduced CD163 expression in CD4+ T lymphocyte-rich microenvironments [13].
• Despite similar lymphocyte numbers, activated lymphocytes (CD69+) were significantly decreased in SpA versus RA patients, with an inverse correlation between CD163 and CD69 levels [1].

Associations of CD163 with chemical compounds

• OBJECTIVE: The cell surface glycoprotein CD163 is a member of the cysteine-rich scavenger receptor family, highly specific for leukocytes of the mononuclear phagocyte lineage [13].
• We found that in a dose-dependent manner soluble CD163 induces a decrease in CD69 expression, a reduced [(3)H]thymidine uptake and a down-regulated matrix metalloproteinase-9 RNA expression in phorbol myristate acetate-stimulated T-cells [14].
• Cross-reactivity could be shown for anti-human CD14, CD163 and mannose receptor (CD206) mAbs [15].
• Studies using the inhibitor TAPI-0 indicate that a metalloproteinase is responsible for LPS-mediated shedding of CD163 [4].
• CD163 is a recently identified member of the scavenger receptor cysteine-rich superfamily, which is expressed on peripheral blood monocytes and most tissue macrophages and is thought to play an important role in the regulation of the inflammatory response of these cells [12].

Physical interactions of CD163

• Its function has remained unknown until recently when CD163 was identified as the endocytic receptor binding hemoglobin (Hb) in complex with the plasma protein haptoglobin (Hp) [16].

Enzymatic interactions of CD163

• Furthermore, we demonstrated that the cytoplasmic domains of CD163 variants are phosphorylated by PKC-alpha in vitro [12].

Regulatory relationships of CD163

• CD163 expression is significantly upregulated by glucocorticoids and IL-10 [17].
• The protein products of the two different haptoglobin alleles differ in their ability to serve as an antioxidant against hemoglobin and also to activate the CD163 receptor [18].
• However, not all CD163-positive cells expressed CCR2, which could be interpreted as a mechanism for retaining the macrophages in the skin [19].
• De novo protein synthesis was not required for this inhibition, suggesting that TGF-beta regulates CD163 expression transcriptionally [20].
• Concomitant treatment with IL-4/dexamethasone up-regulated significantly the expression of CD163 [21].

Other interactions of CD163

• CONCLUSION: Within RA synovium, CD163 has major advantages as a macrophage marker and does not appear to be restricted to "mature" macrophages [13].
• CD163: a signal receptor scavenging haptoglobin-hemoglobin complexes from plasma [16].
• The clinical marker that was most associated with serum levels of soluble CD163 was levels of CRP [22].
• The CD163 expression is induced by interleukin-6, interleukin-10 and glucocorticoids [16].
• We conclude that CD163 has at least two distinct functions: the clearance of hemoglobin in its cell-bound form and participation in anti-inflammation as a soluble factor, exhibiting cytokine-like functions [14].

Analytical, diagnostic and therapeutic context of CD163

• Levels of soluble CD163 in sera and fluids from RA patients were examined by a sandwich enzyme immunoassay and Western blotting [22].
• Double immunofluorescence was performed using antibodies against mPGES-1, COX-1, COX-2, and CD163 [23].
• We report a rapid and highly reproducible rise in soluble CD163 in the plasma of human volunteers given intravenous lipopolysaccharide (LPS) [4].
• Development of an ELISA to measure soluble CD163 in biological fluids [24].
• 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 [25].

References