RED CELLS Identification of the receptor scavenging hemopexin-heme complexes
نویسندگان
چکیده
Heme released from heme-binding proteins on internal hemorrhage, hemolysis, myolysis, or other cell damage is highly toxic due to oxidative and proinflammatory effects. Complex formation with hemopexin, the high-affinity heme-binding protein in plasma and cerebrospinal fluid, dampens these effects and is suggested to facilitate cellular heme metabolism. Using a ligand-affinity approach, we purified the human hemopexin-heme receptor and identified it as the low-density lipoprotein receptor-related protein (LRP)/ CD91, a receptor expressed in several cell types including macrophages, hepatocytes, neurons, and syncytiotrophoblasts. Binding experiments, including Biacore analysis, showed that hemopexinheme complex formation elicits the high receptor affinity. Uptake studies of radiolabeled hemopexin-heme complex in LRP/ CD91-expressing COS cells and confocal microscopy of the cellular processing of fluorescent hemopexin-heme complex established the ability of LRP/CD91 to mediate hemopexin-heme internalization resulting in cellular heme uptake and lysosomal hemopexin degradation. Uptake of hemopexin-heme complex induced LRP/CD91-dependent heme-oxygenase 1 mRNA transcription in cultured monocytes. In conclusion, hemopexin-heme complexes are removed by a receptor-mediated pathway showing striking similarities to the CD163-mediated haptoglobin-hemoglobin clearance in macrophages. Furthermore, the data indicate a hitherto unknown role of LRP/CD91 in inflammation. (Blood. 2005; 106:2572-2579)
منابع مشابه
Identification of the Receptor Scavenging Hemopexin- Heme Complexes Running title: Identification of the Hemopexin-Heme Receptor
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Identification of the receptor scavenging hemopexin-heme complexes.
Heme released from heme-binding proteins on internal hemorrhage, hemolysis, myolysis, or other cell damage is highly toxic due to oxidative and proinflammatory effects. Complex formation with hemopexin, the high-affinity heme-binding protein in plasma and cerebrospinal fluid, dampens these effects and is suggested to facilitate cellular heme metabolism. Using a ligand-affinity approach, we puri...
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