The alpha(1,3)fucosyltransferase Fuc-TVII controls leukocyte trafficking through an essential role in L-, E-, and P-selectin ligand biosynthesis

  • Cell. 1996 Aug 23;86(4):643-53. doi: 10.1016/s0092-8674(00)80137-3.
P Malý  1 ,  A Thall ,  B Petryniak ,  C E Rogers ,  P L Smith ,  R M Marks ,  R J Kelly ,  K M Gersten ,  G Cheng ,  T L Saunders ,  S A Camper ,  R T Camphausen ,  F X Sullivan ,  Y Isogai ,  O Hindsgaul ,  U H von Andrian ,  J B Lowe
Affiliations
  • 1. Howard Hughes Medical Institute, University of Michigan Medical School, Ann Arbor 48109-0650, USA.
Abstract

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.