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Heme carrier protein (HCP‐1) spatially interacts with the CD163 hemoglobin uptake pathway and is a target of inflammatory macrophage activation
Author(s) -
Schaer Christian A.,
Vallelian Florence,
Imhof Alexander,
Schoedon Gabriele,
Schaer Dominik J.
Publication year - 2008
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0407226
Subject(s) - cd163 , biology , macrophage , heme , hemoglobin , microbiology and biotechnology , inflammation , biophysics , immunology , biochemistry , enzyme , in vitro
Macrophages constitute the major cellular compartment for hemoglobin (Hb) degradation and subsequent recycling of heme‐iron to erythropoiesis. Dysregulation of macrophage iron and heme metabolism is a major pathophysiologic determinant of anemia of chronic disease. In this study, we show that the heme transporter heme carrier protein 1 (HCP‐1) is expressed in human macrophages. Within early endosomes, HCP‐1 colocalizes with endocytosed Hb‐haptoglobin (Hp) complexes, which are taken up via the CD163 scavenger receptor pathway. Hb‐Hp passes the divalent metal transporter 1B/HCP‐1‐positive endosomal compartment on its route from the cell surface to lysosomes. HCP‐1 mRNA and protein expression are down‐regulated by stimulation of macrophages with various TLR agonists and IFN‐γ. The profound suppression of HCP‐1 expression by inflammatory macrophage activation parallels the regulation of the iron exporter ferroportin. In contrast, dexamethasone enhanced HCP‐1 expression significantly. Given the spatial relationship, we propose that the Hb scavenger receptor CD163 and HCP‐1 constitute a linked pathway for Hb catabolism and heme‐iron recycling in human macrophages.