CD163-expressing monocytes constitute an endotoxin-sensitive Hb clearance compartment within the vascular system.
Hemoglobin (Hb) is released into the circulation during intravascular hemolysis and exerts toxic effects through oxidative damage and NO scavenging. According to the traditional concept of Hb clearance, free Hb is bound to the plasma protein haptoglobin (Hp), and the Hb-Hp complexes are cleared by liver and spleen macrophages via the Hb scavenger receptor CD163. Using a novel whole blood assay, we demonstrate that clearance of Hb-Hp is also mediated by CD14(high)/CD64(high) peripheral blood monocytes, which express CD163. Hb-Hp uptake by these cells is Ca(2+)-dependent and is abrogated by the addition of CD163-blocking antibodies. Accordingly, LPS treatment reduces monocyte surface CD163 and impairs Hb-Hp uptake. Monocytes likely mediate Hp-Hb uptake in vivo, as a high expression of the heme breakdown enzyme heme oxygenase-1 was observed in CD163(+) monocytes but not in other leukocyte populations obtained from healthy blood donors. We propose that CD163-mediated Hb-Hp uptake by peripheral blood monocytes constitutes an Hb-Hp clearance pathway, which acts at the site of intravascular hemolysis to reduce Hb-Hp circulation time and toxicity. Disruption of monocyte Hb-Hp clearance may increase Hb-Hp toxicity and contribute to the pathogenesis of systemic inflammatory diseases associated with reduced monocyte CD163 expression.
Schaer
Christian A
CA
Department of Medicine, University Hospital, CH-8091 Zurich, Switzerland.
Vallelian
Florence
F
Imhof
Alexander
A
Schoedon
Gabriele
G
Schaer
Dominik J
DJ
D015703:Antigens, CD / Q000502:physiology*; D015214:Antigens, Differentiation, Myelomonocytic / Q000502:physiology*; D001808:Blood Vessels; D006242:Haptoglobins / Q000378:metabolism*; D006454:Hemoglobins / Q000378:metabolism*; D006461:Hemolysis; D006801:Humans; D007249:Inflammation / Q000209:etiology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009000:Monocytes / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000502:physiology*; D000098902:CD163 Antigen
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D006242:Haptoglobins; D006454:Hemoglobins; D008070:Lipopolysaccharides; D011956:Receptors, Cell Surface