The FX enzyme is a functional component of lymphocyte activation.
Fucose is an essential constituent of selectin ligands. These molecules mediate the initial contact between extravasating leukocytes and endothelial cells. The generation of GDP-L-fucose by the FX enzyme is the final step of fucose biosynthesis. Recently, we demonstrated that outside-in signaling regulates the expression of the FX enzyme in certain cancer cells. The present study demonstrates that the polyclonal activation of T and B cells significantly up-regulated the expression of the FX enzyme and of the fucosylated selectin ligands sLe-x and CLA. Treatment of T cells with FX antisense oligonucleotides significantly decreased selectin ligand expression upon activation. We conclude that FX is regulated by outside-in signals also in lymphocytes and that this enzyme is involved in the biosynthesis of selectin ligands in such cells. We propose that FX takes part in the cascade of events leading to the extravasation of activated lymphocytes.
Eshel
R
R
Department of Cell Research and Immunology, Tel Aviv University, Tel Aviv, Israel.
Besser
M
M
Zanin
A
A
Sagi-Assif
O
O
Witz
I P
IP
D018941:Antigens, CD19; D001402:B-Lymphocytes / Q000166:cytology / Q000201:enzymology* / Q000276:immunology; D015415:Biomarkers; D018395:CA-19-9 Antigen; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000201:enzymology* / Q000276:immunology; D002238:Carbohydrate Epimerases / Q000235:genetics*; D002478:Cells, Cultured; D004789:Enzyme Activation; D005732:Gangliosides / Q000096:biosynthesis*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D006836:Hydro-Lyases / Q000235:genetics*; D008024:Ligands; D008213:Lymphocyte Activation / Q000502:physiology*; D020319:Oligodeoxyribonucleotides, Antisense; D009844:Oligosaccharides / Q000096:biosynthesis*; D012333:RNA, Messenger; D019087:Selectins / Q000378:metabolism; D000080506:Sialyl Lewis X Antigen; D015854:Up-Regulation
D018941:Antigens, CD19; D015415:Biomarkers; D018395:CA-19-9 Antigen; D005732:Gangliosides; D008024:Ligands; D020319:Oligodeoxyribonucleotides, Antisense; D009844:Oligosaccharides; D012333:RNA, Messenger; D019087:Selectins; D000080506:Sialyl Lewis X Antigen; C064564:sialyl Le(a) ganglioside; D006836:Hydro-Lyases; C044971:GDPmannose 4,6-dehydratase; D002238:Carbohydrate Epimerases