The sialomucin CD164 (MGC-24v) is an adhesive glycoprotein expressed by human hematopoietic progenitors and bone marrow stromal cells that serves as a potent negative regulator of hematopoiesis.
Mucin-like molecules represent an emerging family of cell surface glycoproteins expressed by cells of the hematopoietic system. We report the isolation of a cDNA clone that encodes a novel transmembrane isoform of the mucin-like glycoprotein MGC-24, expressed by both hematopoietic progenitor cells and elements of the bone marrow (BM) stroma. This molecule was clustered as CD164 at the recent workshop on human leukocyte differentiation antigens. CD164 was identified using a retroviral expression cloning strategy and two novel monoclonal antibody (MoAb) reagents, 103B2/9E10 and 105.A5. Both antibodies detected CD164/MGC-24v protein expression by BM stroma and subpopulations of the CD34(+) cells, which include the majority of clonogenic myeloid (colony-forming unit-granulocyte-macrophage [CFU-GM]) and erythroid (blast-forming unit-erythroid [BFU-E]) progenitors and the hierarchically more primitive precursors (pre-CFU). Biochemical and functional characterization of CD164 showed that this protein represents a homodimeric molecule of approximately 160 kD. Functional studies demonstrate a role for CD164 in the adhesion of hematopoietic progenitor cells to BM stromal cells in vitro. Moreover, antibody ligation of CD164 on primitive hematopoietic progenitor cells characterized by the cell surface phenotype CD34(BRIGHT)CD38(-) results in the decreased recruitment of these cells into cell cycle, suggesting that CD164 represents a potent signaling molecule with the capacity to suppress hematopoietic cell proliferation.
Zannettino
A C
AC
Hanson Centre for Cancer Research, Matthew Roberts Laboratory, Institute Of Medical and Veterinary Science, Adelaide, Australia. andrew.zannettino@imvs.sa.gov.au
Bühring
H J
HJ
Niutta
S
S
Watt
S M
SM
Benton
M A
MA
Simmons
P J
PJ
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D018952:Antigens, CD34 / Q000032:analysis; D001483:Base Sequence; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology*; D002448:Cell Adhesion; D002450:Cell Communication; D002455:Cell Division; D019070:Cell Lineage; D002478:Cells, Cultured; D003001:Cloning, Molecular; D019281:Dimerization; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D017154:Stromal Cells / Q000166:cytology / Q000502:physiology
D000911:Antibodies, Monoclonal; D018952:Antigens, CD34; D011956:Receptors, Cell Surface; C085661:mucin receptor