The alpha(1,3)fucosyltransferases FucT-IV and FucT-VII exert collaborative control over selectin-dependent leukocyte recruitment and lymphocyte homing.
E-, P-, and L-selectin counterreceptor activities, leukocyte trafficking, and lymphocyte homing are controlled prominently but incompletely by alpha(1,3)fucosyltransferase FucT-VII-dependent fucosylation. Molecular determinants for FucT-VII-independent leukocyte trafficking are not defined, and evidence for contributions by or requirements for other FucTs in leukocyte recruitment is contradictory and incomplete. We show here that inflammation-dependent leukocyte recruitment retained in FucT-VII deficiency is extinguished in FucT-IV(-/-)/FucT-VII(-/-) mice. Double deficiency yields an extreme leukocytosis characterized by decreased neutrophil turnover and increased neutrophil production. FucT-IV also contributes to HEV-born L-selectin ligands, since lymphocyte homing retained in FucT-VII(-/-) mice is revoked in FucT-IV(-/-)/FucT-VII(-/-) mice. These observations reveal essential FucT-IV-dependent contributions to E-, P-, and L-selectin ligand synthesis and to the control of leukocyte recruitment and lymphocyte homing.
Homeister
J W
JW
Howard Hughes Medical Institute, The University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Thall
A D
AD
Petryniak
B
B
Malý
P
P
Rogers
C E
CE
Smith
P L
PL
Kelly
R J
RJ
Gersten
K M
KM
Askari
S W
SW
Cheng
G
G
Smithson
G
G
Marks
R M
RM
Misra
A K
AK
Hindsgaul
O
O
von Andrian
U H
UH
Lowe
J B
JB
D000818:Animals; D002465:Cell Movement; D002874:Chromosome Mapping; D005260:Female; D005647:Fucosyltransferases / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007958:Leukocyte Count; D007962:Leukocytes / Q000502:physiology*; D008214:Lymphocytes / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D019087:Selectins / Q000502:physiology*
D019087:Selectins; D005647:Fucosyltransferases; C031692:galactoside 3-fucosyltransferase