Enforced fucosylation of neonatal CD34+ cells generates selectin ligands that enhance the initial interactions with microvessels but not homing to bone marrow.
Hematopoietic progenitor/stem cell homing to the bone marrow requires the concerted action of several adhesion molecules. Endothelial P- and E-selectins play an important role in this process, but their ligands on a large subset of neonate-derived human CD34+ cells are absent, leading to a reduced ability to interact with the bone marrow (BM) microvasculature. We report here that this deficiency results from reduced alpha1,3-fucosyltransferase (FucT) expression and activity in these CD34+ cells. Incubation of CD34+ cells with recombinant human FucTVI rapidly corrected the deficiency in nonbinding CD34+ cells and further increased the density of ligands for both P- and E-selectins on all cord blood-derived CD34+ cells. Intravital microscopy studies revealed that these FucTVI-treated CD34+ cells displayed a marked enhancement in their initial interactions with the BM microvasculature, but unexpectedly, homing into the BM was not improved by FucTVI treatment. These data indicate that, although exogenous FucT enzyme activity can rapidly modulate selectin binding avidity of cord blood CD34+ cells, further studies are needed to understand how to translate a positive effect on progenitor cell adhesion in bone marrow microvessels into one that significantly influences migration and lodgement into the parenchyma.
Hidalgo
Andrés
A
Department of Medicine and Immunobiology Center, Mount Sinai School of Medicine, New York, NY 10029, USA.
Frenette
Paul S
PS
D000818:Animals; D000831:Animals, Newborn; D018952:Antigens, CD34 / Q000378:metabolism; D001853:Bone Marrow / Q000098:blood supply; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D018395:CA-19-9 Antigen; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D019040:E-Selectin / Q000378:metabolism*; D005312:Fetal Blood / Q000166:cytology; D005643:Fucose / Q000378:metabolism*; D005647:Fucosyltransferases / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D005732:Gangliosides / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008833:Microcirculation; D019007:P-Selectin / Q000378:metabolism*
D018952:Antigens, CD34; D018395:CA-19-9 Antigen; D019040:E-Selectin; D005732:Gangliosides; D008024:Ligands; D019007:P-Selectin; D005643:Fucose; C064564:sialyl Le(a) ganglioside; D005647:Fucosyltransferases; C031692:galactoside 3-fucosyltransferase