Cd44 Is a Major E-Selectin Ligand on Human Hematopoietic Progenitor Cells

doi:10.1083/jcb.153.6.1277

Published online 11 June 2001. doi:10.1083/jcb.153.6.1277

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© The Rockefeller University Press, 0021-9525/2001//1277 $5.00
The Journal of Cell Biology, Volume 153, Number 6, , 2001 1277-1286

Original Article

Cd44 Is a Major E-Selectin Ligand on Human Hematopoietic Progenitor Cells

Charles J. Dimitroff^a^,d, Jack Y. Lee^a^,d, Shahin Rafii^e, Robert C. Fuhlbrigge^a^,d, and Robert Sackstein^a^,b^,c^,d

^a Department of Dermatology, Brigham and Women's Hospital, Boston, Massachusetts 02115
^b Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115
^c Bone Marrow Transplant Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114
^d Harvard Skin Disease Research Center, Harvard Medical School, Boston, Massachusetts, 02115
^e Division of Hematology-Oncology, New York Hospital Cornell Medical Center, New York, New York 10021
Harvard Institutes of Medicine, 77 Ave. Louis Pasteur, Room 671, Boston, MA 02115.(617) 525-5571(617) 525-5601

rsackstein{at}rics.bwh.harvard.edu

E-selectin plays a critical role in mediating tissue-specifichoming of T cells into skin, and of primitive hematopoieticprogenitor cells (HPCs) into bone marrow (BM). Though it isknown that a glycoform of PSGL-1 (CLA) functions as the principalE-selectin ligand on human T lymphocytes, the E-selectin ligand(s)of human HPCs has not been identified. We used a shear-basedadherence assay to analyze and define the E-selectin ligandactivity of membrane proteins from human HPCs. Our data showthat PSGL-1 expressed on human HPCs is an E-selectin ligand,and that HPCs also express a previously unrecognized E-selectinligand, CD44. The E-selectin ligand activity of CD44 is conferredby the elaboration of sialylated, fucosylated binding determinantson N-glycans. This glycoform of CD44 is expressed on primitiveCD34+ human HPCs, but not on more mature hematopoietic cells.Under physiologic flow conditions, this molecule mediates E-selectin–dependentrolling interactions over a wider shear range than that of PSGL-1,and promotes human HPC rolling interactions on E-selectin expressedon human BM endothelial cells. These findings offer new insightsinto the structural biology and physiology of CD44, and intothe molecular basis of E-selectin–dependent adhesive interactionsthat direct homing of human HPC to BM.

Key Words: hematopoietic stem cells • E-selectin • CD44 • PSGL-1 • CLA

Abbreviations used in this paper: AML, acute myelogenous leukemia;AP, alkaline phosphatase; BM, bone marrow; BMEC-1, BM endothelialcell line-1; CLA, cutaneous lymphocyte antigen; HA, hyaluronicacid; HCELL, hematopoietic cell E-/L-selectin ligand; HPC, hematopoieticprogenitor cell; OSGE, O-sialoglycoprotein endopeptidase; PSGL-1,P-selectin glycoprotein ligand 1; PVDF, polyvinylidene difluoride;VCAM, vascular cell adhesion molecule; VLA, very late antigen.

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