Surface fucosylation of human cord blood cells augments binding to P-selectin and E-selectin and enhances engraftment in bone marrow.
Murine hematopoietic stem and progenitor cells (HSPCs) home to bone marrow in part by rolling on P-selectin and E-selectin expressed on endothelial cells. Human adult CD34(+) cells, which are enriched in HSPCs, roll on endothelial selectins in bone marrow vessels of nonobese diabetic/severe combined immune deficiency (NOD/SCID) mice. Many human umbilical cord blood (CB) CD34(+) cells do not roll in these vessels, in part because of an uncharacterized defect in binding to P-selectin. Selectin ligands must be alpha1-3 fucosylated to form glycan determinants such as sialyl Lewis x (sLe(x)). We found that inadequate alpha1-3 fucosylation of CB CD34(+) cells, particularly CD34(+)CD38(-/low) cells that are highly enriched in HSPCs, caused them to bind poorly to E-selectin as well as to P-selectin. Treatment of CB CD34(+) cells with guanosine diphosphate (GDP) fucose and exogenous alpha1-3 fucosyltransferase VI increased cell-surface sLe(x) determinants, augmented binding to fluid-phase P- and E-selectin, and improved cell rolling on P- and E-selectin under flow. Similar treatment of CB mononuclear cells enhanced engraftment of human hematopoietic cells in bone marrows of irradiated NOD/SCID mice. These observations suggest that alpha1-3 fucosylation of CB cells might be a simple and effective method to improve hematopoietic cell homing to and engraftment in bone marrows of patients receiving CB transplants.
Xia
Lijun
L
Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, OK 73104, USA. lijun-xia@omrf.ouhsc.edu.
McDaniel
J Michael
JM
Yago
Tadayuki
T
Doeden
Andrea
A
McEver
Rodger P
RP
D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D016026:Bone Marrow Transplantation; D002448:Cell Adhesion; D019040:E-Selectin / Q000378:metabolism*; D000939:Epitopes; D005260:Female; D005312:Fetal Blood / Q000166:cytology*; D005643:Fucose / Q000378:metabolism*; D005647:Fucosyltransferases / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D036904:Leukocyte Rolling; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism; D016256:Lewis X Antigen / Q000378:metabolism; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D019007:P-Selectin / Q000378:metabolism*; D013047:Specific Pathogen-Free Organisms
D018952:Antigens, CD34; D019040:E-Selectin; D000939:Epitopes; D016256:Lewis X Antigen; D019007:P-Selectin; D005643:Fucose; D005647:Fucosyltransferases; C019818:3-galactosyl-N-acetylglucosaminide 4-alpha-L-fucosyltransferase