In vitro homing of hemopoietic stem cells is mediated by a recognition system with galactosyl and mannosyl specificities

Abstract

We synthesized a number of neoglycoprotein probes by covalently linking three biologically relevant sugars (mannose, galactose, and fucose) to a protein molecule so as to retain the pyranose (ring) form of sugars necessary for their interaction with lectins. In the presence of galactosyl and mannosyl but not fucosyl probes, the production of CFU-S [colony-forming unit(s) in spleen] and total cells was halted in murine long-term marrow cultures. Cobblestone areas disappeared in these cultures, indicating the inhibition of binding of hemopoietic cells to the stroma. Electron microscopy revealed no alterations of the stroma, and the probes did not have direct cytotoxic or inhibitory effects on the growth of CFU-S or CFU-C [colony-forming unit(s) in culture]. Stroma grown for 5 weeks in the presence of the probes could subsequently support the growth of hemopoietic progenitor cells when the probes were removed from the medium. Conversely, the proliferative capacity of CFU-S in the supernate, grown in the presence of the probes, was retained upon grafting to control stroma. Galactosyl and mannosyl but not fucosyl probes differentially agglutinated CFU-S in whole-marrow-cell suspensions, suggesting the presence of membrane lectins with specificity for these sugars on the surface of CFU-S. We conclude that the binding of CFU-S to marrow stroma (homing) is mediated by a recognition system with galactosyl and mannosyl specificities.