CD44 is a major E-selectin ligand on human hematopoietic progenitor cells.
E-selectin plays a critical role in mediating tissue-specific homing of T cells into skin, and of primitive hematopoietic progenitor cells (HPCs) into bone marrow (BM). Though it is known that a glycoform of PSGL-1 (CLA) functions as the principal E-selectin ligand on human T lymphocytes, the E-selectin ligand(s) of human HPCs has not been identified. We used a shear-based adherence assay to analyze and define the E-selectin ligand activity of membrane proteins from human HPCs. Our data show that PSGL-1 expressed on human HPCs is an E-selectin ligand, and that HPCs also express a previously unrecognized E-selectin ligand, CD44. The E-selectin ligand activity of CD44 is conferred by the elaboration of sialylated, fucosylated binding determinants on N-glycans. This glycoform of CD44 is expressed on primitive CD34+ human HPCs, but not on more mature hematopoietic cells. Under physiologic flow conditions, this molecule mediates E-selectin-dependent rolling interactions over a wider shear range than that of PSGL-1, and promotes human HPC rolling interactions on E-selectin expressed on human BM endothelial cells. These findings offer new insights into the structural biology and physiology of CD44, and into the molecular basis of E-selectin-dependent adhesive interactions that direct homing of human HPC to BM.
Dimitroff
C J
CJ
Department of Dermatology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Lee
J Y
JY
Rafii
S
S
Fuhlbrigge
R C
RC
Sackstein
R
R
D000818:Animals; D015153:Blotting, Western / Q000379:methods; D016466:CHO Cells; D006224:Cricetinae; D019040:E-Selectin / Q000235:genetics / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D018922:HL-60 Cells; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism*; D020014:K562 Cells; D008024:Ligands; D008562:Membrane Glycoproteins / Q000378:metabolism; D019007:P-Selectin / Q000378:metabolism; D012967:Sodium Dodecyl Sulfate
D019040:E-Selectin; D018960:Hyaluronan Receptors; D008024:Ligands; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D012967:Sodium Dodecyl Sulfate