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 PKCalpha 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.
Matthews
Kathryn E
KE
Hemosol LP, Mississauga, ON, Canada L5N 8H9.
Mueller
Susan G
SG
Woods
Caroline
C
Bell
David N
DN
D017398:Alternative Splicing; D015703:Antigens, CD / Q000097:blood*; D018952:Antigens, CD34 / Q000097:blood; D015214:Antigens, Differentiation, Myelomonocytic / Q000097:blood*; D001483:Base Sequence; D001854:Bone Marrow Cells / Q000502:physiology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D015672:Erythroid Precursor Cells / Q000502:physiology*; D015870:Gene Expression; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D011956:Receptors, Cell Surface / Q000097:blood* / Q000378:metabolism*; D017385:Sequence Homology; D014470:Umbilical Cord / Q000166:cytology; D000098902:CD163 Antigen
D015703:Antigens, CD; D018952:Antigens, CD34; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D011956:Receptors, Cell Surface; C027079:hemoglobin-haptoglobin receptor