CD44 is a major E-selectin ligand on human hematopoietic progenitor cells

被引:240
|
作者
Dimitroff, CJ
Lee, JY
Rafii, S
Fuhlbrigge, RC
Sackstein, R
机构
[1] Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA
[2] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA
[3] Massachusetts Gen Hosp, Dept Med, Bone Marrow Transplant Unit, Boston, MA 02114 USA
[4] Harvard Univ, Sch Med, Skin Dis Res Ctr, Boston, MA 02115 USA
[5] Cornell Univ, Med Ctr, New York Hosp, Div Hematol Oncol, New York, NY 10021 USA
来源
JOURNAL OF CELL BIOLOGY | 2001年 / 153卷 / 06期
关键词
hematopoietic stem cells; E-selectin; CD44; PSGL-1; CLA;
D O I
10.1083/jcb.153.6.1277
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:1277 / 1286
页数:10
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