Enzymic control of the expression of the X determinant (CD15) in human myeloid cells during maturation: the regulatory role of 6-sialytransferase.
To establish the basis for the reduced expression of the X determinant on leukemic blasts and the changes in antigenic expression that occur during myeloid maturation, the presence on myeloid cells of X and related structures was examined in conjunction with studies on the activities of the glycosyltransferases involved in their biosynthesis. Expression of X and sialyl-X was weak on blasts in comparison with neutrophils despite the presence of the requisite precursor structures. Much higher levels of 3-fucosyltransferase activity were found in blasts than in neutrophils when nonsialylated substrates were used, but, whereas the enzyme in neutrophils reacted equally well with 3'-sialylated and nonsialylated acceptors, the enzyme in blasts showed a marked preference for nonsialylated substrates. 6'-Sialyltransferase activity was strong in blasts but was not detectable in neutrophils, whereas a much lower level of 3'-sialyltransferase activity was present in both blasts and neutrophils. Dimethyl sulfoxide-induced maturation of HL60 cells was associated with (1) a decrease in both 6'-sialyltransferase and 3-fucosyltransferase activities, (2) a change in the substrate specificity of 3-fucosyltransferase towards that found in mature cells, and (3) increased cell surface expression of sialyl-X. These results suggest that the reduced expression of X in myeloblasts is related to the presence of the strong 6'-sialyltransferase, which uses the precursor substrate at the expense of the 3-fucosyltransferase and prevents the synthesis of X and sialyl-X. The developmental regulation of the levels of 3'- and 6'-sialyltransferases, and the level and specificity of the 3-fucosyltransferases, therefore controls the expression of X and its degree of sialylation.
Division of Immunochemical Genetics and MRC Clinical Research Centre, Middlesex, UK.
P O
PO
Skacel
A J
AJ
Edwards
C T
CT
Harrison
W M
WM
Watkins
D000208:Acute Disease; D015703:Antigens, CD / Q000096:biosynthesis*; D002454:Cell Differentiation / Q000187:drug effects; D004121:Dimethyl Sulfoxide; D004790:Enzyme Induction; D006801:Humans; D007951:Leukemia, Myeloid / Q000276:immunology / Q000378:metabolism*; D016256:Lewis X Antigen; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism*; D012799:Sialyltransferases / Q000032:analysis / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured / Q000276:immunology / Q000378:metabolism; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase
D015703:Antigens, CD; D016256:Lewis X Antigen; D012799:Sialyltransferases; D004121:Dimethyl Sulfoxide; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase; C000722087:ST3GAL1 protein, human