Downregulation of the selectin ligand-producing fucosyltransferases Fuc-TIV and Fuc-TVII during foam cell formation in monocyte-derived macrophages.
Identification of genes expressed during foam cell formation is important for understanding the molecular basis of atherosclerosis. We used polymerase chain reaction (PCR)-based differential display to isolate differentially expressed cDNA species in foam cells induced by incubation of human monocyte-derived macrophages in the presence of acetylated or oxidized LDL. This led to identification of a 306-bp cDNA with 100% homology to type IV fucosyltransferase (Fuc-TIV), which was downregulated by factors of 20 and 3 in acetylated LDL- and oxidized LDL-loaded macrophages, respectively. This enzyme is sufficient for the expression of Lewis X and sialyl Lewis X, carbohydrate adhesion molecules that bind to receptors of the selectin family. Expression of a second fucosyltransferase (Fuc-TVII) that synthesizes sialyl Lewis X but not Lewis X was shown by quantitative reverse transcription-PCR to also be reduced, by 40% and 20% in acetylated LDL- and oxidized LDL-loaded macrophages, respectively. alpha-(1,3)-Fucosyltransferase enzyme activity was reduced in lysates from both acetylated LDL- and oxidized LDL-loaded cells. Analysis by flow cytometry showed reduced expression of the CD15 (corresponding to Lewis X) and CD15s (sialyl Lewis X) antigens on the surface of cells loaded with either acetylated or oxidized LDL. Transformation of macrophages into foam cells results in reduced expression of selectin-binding ligands on the surface of such cells.
Cullen
P
P
Institut für Arterioskleroseforschung, Westfälische Wilhelms-Universität Münster, Germany. cullen@uni-muenster.de
Mohr
S
S
Brennhausen
B
B
Cignarella
A
A
Assmann
G
G
D000107:Acetylation; D015152:Blotting, Northern; D002478:Cells, Cultured; D008078:Cholesterol, LDL / Q000378:metabolism; D018076:DNA, Complementary / Q000032:analysis; D015536:Down-Regulation; D005487:Foam Cells / Q000378:metabolism*; D005647:Fucosyltransferases / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D016256:Lewis X Antigen / Q000032:analysis; D008024:Ligands; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology*; D010084:Oxidation-Reduction; D016133:Polymerase Chain Reaction / Q000379:methods; D012194:RNA-Directed DNA Polymerase; D019087:Selectins / Q000502:physiology*; D012689:Sequence Homology, Nucleic Acid
D008078:Cholesterol, LDL; D018076:DNA, Complementary; D016256:Lewis X Antigen; D008024:Ligands; D019087:Selectins; D005647:Fucosyltransferases; C031692:galactoside 3-fucosyltransferase; D012194:RNA-Directed DNA Polymerase