Expression of the Hemoglobin-Haptoglobin Receptor CD163 on Hematopoietic Progenitors

CD163, the hemoglobin-haptoglobin receptor, has been reported to be expressed exclusively on monocyte/ macrophages. Here we demonstrate that CD163 is also expressed by a subpopulation of hematopoietic stem/progenitor cells. Flow cytometric analysis shows that 1.9 ± 1.3% (±SD, n = 16) of adult bone marrow and 2.0 ± 1.8% (n = 8) of umbilical cord blood CD34⁺ cells express cell-surface CD163, and 69.1 ± 16.9% (n = 9) and 79.7 ± 22.4% (n = 8) of the respective cells contain the CD163 protein intracellularly. The expression of CD163 by CD34⁺ cells was confirmed by western blot analysis of cell lysates. Transcripts corresponding to the known predominant and variant 1 forms of CD163 were amplified via RT-PCR from CD34⁺ cell-derived mRNA. A new variant (K11) with a deletion at the start of exon 15 was also detected. The deleted region contains a PKCα phosphorylation site and an amino acid sequence (YREM) that may support efficient receptor endocytosis. The addition of activating anti-CD163 antibodies increased the growth and differentiation of erythroid progenitors in colony-forming assays. These data suggest that hemoglobin may mediate a stimulatory effect on erythropoiesis through the activation of CD163 on hematopoietic progenitor cells.