title: The alpha(1,3)fucosyltransferases FucT-IV and FucT-VII exert collaborative control over selectin-dependent leukocyte recruitment and lymphocyte homing.
abstract: 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.
authors.affiliation: Howard Hughes Medical Institute, The University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: J W
authors.initials: JW
authors.lastname: Homeister
authors.forename: A D
authors.initials: AD
authors.lastname: Thall
authors.forename: B
authors.initials: B
authors.lastname: Petryniak
authors.forename: P
authors.initials: P
authors.lastname: Malý
authors.forename: C E
authors.initials: CE
authors.lastname: Rogers
authors.forename: P L
authors.initials: PL
authors.lastname: Smith
authors.forename: R J
authors.initials: RJ
authors.lastname: Kelly
authors.forename: K M
authors.initials: KM
authors.lastname: Gersten
authors.forename: S W
authors.initials: SW
authors.lastname: Askari
authors.forename: G
authors.initials: G
authors.lastname: Cheng
authors.forename: G
authors.initials: G
authors.lastname: Smithson
authors.forename: R M
authors.initials: RM
authors.lastname: Marks
authors.forename: A K
authors.initials: AK
authors.lastname: Misra
authors.forename: O
authors.initials: O
authors.lastname: Hindsgaul
authors.forename: U H
authors.initials: UH
authors.lastname: von Andrian
authors.forename: J B
authors.initials: JB
authors.lastname: Lowe
mesh_terms: 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*
chemical_list: D019087:Selectins; D005647:Fucosyltransferases; C031692:galactoside 3-fucosyltransferase