The alpha(1,3)fucosyltransferase Fuc-TVII controls leukocyte trafficking through an essential role in L-, E-, and P-selectin ligand biosynthesis.
alpha(1,3)Fucosylated oligosaccharides represent components of leukocyte counterreceptors for E- and P-selectins and of L-selectin ligands expressed by lymph node high endothelial venules (HEV). The identity of the alpha(1,3)fucosyltransferase(s) required for their expression has been uncertain, as has a requirement for alpha(1,3)fucosylation in HEV L-selectin ligand activity. We demonstrate here that mice deficient in alpha(1,3) fucosyltransferase Fuc-TVII exhibit a leukocyte adhesion deficiency characterized by absent leukocyte E- and P-selectin ligand activity and deficient HEV L-selectin ligand activity. Selectin ligand deficiency is distinguished by blood leukocytosis, impaired leukocyte extravasation in inflammation, and faulty lymphocyte homing. These observations demonstrate an essential role for Fuc-TVII in E-, P-, and L-selectin ligand biosynthesis and imply that this locus can control leukocyte trafficking in health and disease.
Malý
P
P
Howard Hughes Medical Institute, University of Michigan Medical School, Ann Arbor 48109-0650, USA.
Thall
A
A
Petryniak
B
B
Rogers
C E
CE
Smith
P L
PL
Marks
R M
RM
Kelly
R J
RJ
Gersten
K M
KM
Cheng
G
G
Saunders
T L
TL
Camper
S A
SA
Camphausen
R T
RT
Sullivan
F X
FX
Isogai
Y
Y
Hindsgaul
O
O
von Andrian
U H
UH
Lowe
J B
JB
D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D002448:Cell Adhesion; D002465:Cell Movement; D002478:Cells, Cultured; D019040:E-Selectin / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000502:physiology*; D005647:Fucosyltransferases / Q000235:genetics*; D006031:Glycosylation; D007158:Immunologic Techniques; D019041:L-Selectin / Q000096:biosynthesis*; D007964:Leukocytosis / Q000235:genetics; D008024:Ligands; D008214:Lymphocytes / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000502:physiology; D019007:P-Selectin / Q000096:biosynthesis*; D011499:Protein Processing, Post-Translational
D000954:Antigens, Surface; D019040:E-Selectin; D008024:Ligands; D019007:P-Selectin; D019041:L-Selectin; D005647:Fucosyltransferases; C031692:galactoside 3-fucosyltransferase