Identification of the haemoglobin scavenger receptor

Abstract

Intravascular haemolysis is a physiological phenomenon as well as a severe pathological complication when accelerated in various autoimmune, infectious (such as malaria) and inherited (such as sickle cell disease) disorders. Haemoglobin released into plasma is captured by the acute phase protein haptoglobin, which is depleted from plasma during elevated haemolysis. Here we report the identification of the acute phase-regulated and signal-inducing macrophage protein, CD163, as a receptor that scavenges haemoglobin by mediating endocytosis of haptoglobin-haemoglobin complexes. CD163 binds only haptoglobin and haemoglobin in complex, which indicates the exposure of a receptor-binding neoepitope. The receptor-ligand interaction is Ca2+-dependent and of high affinity. 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). Specific CD163-mediated endocytosis of haptoglobin-haemoglobin complexes is measurable in cells transfected with CD163 complementary DNA and in CD163-expressing myelo-monocytic lymphoma cells.

Dysregulated iron homeostasis is strongly associated with multiorgan failure and early mortality in acute‐on‐chronic liver failure

“…This has also been conceptualized and validated. 21 A significant increase in intracellular LIP in macrophages was also observed in the nonsurviving ACLF patients.…”

“…18 CD163 on macrophage lineage cells helps in the internalization of circulating (He-Hp) complex resulting in release of bilirubin in the circulation and generation of iron, which is either exported or stored intracellularly as LIP. [19][20][21] Increase in CD163 level correlates with increased incidence of secondary iron overload. 22 Hemosiderosis related to CD163 corresponds to increased toxicity, which may be responsible for high mortality in these patients.…”

Expression profiling of IL‐10‐regulated genes in human monocytes and peripheral blood mononuclear cells from psoriatic patients during IL‐10 therapy

“…It mediates this function at least partially by an increased clearance of pathogens via up-regulation of a whole spectrum of phagocytosis-mediating receptors (FcR, CR1, MARCO, scavenger receptor) and favors resistance to fungal pathogens via up-regulation of pentraxin 3 [26]. Additionally, IL-10 up-regulates receptors for the uptake of autoantigens (CD163) [35] or apoptotic cells (c-mer, Gas6) which would be generated by a destructive immune response against the host. This might be important to avoid the induction of an autoimmune response.…”

A new role for the P2X7 receptor: a scavenger receptor for bacteria and apoptotic cells in the absence of serum and extracellular ATP

“…Macrophages also express scavenger receptors (SR) which are a large group of structurally diverse cell-surface glycoproteins which recognize and endocytose a wide range of particles and molecules. These targets for macrophage SRs include high density lipoprotein (by SR-B1) [6], hemoglobin-haptoglobin complexes (by CD163) [7], β-amyloid deposits (by CD36) [8] and bacteria (by SR-A, SR-B1, CD36, and CD163) [9][10][11]. A broad classification of SR into Class A (triple helix collagenous structure) and Class B (two transmembrane domains) down to Class F has been proposed [12] but this classification does not fully capture the diversity of structural motifs.…”