Reduced phagocytic activity of polymorphonuclear leukocytes in α(1,3) fucosyltransferase VII‐deficient mice

Abstract

Deficiencies in adhesion molecules or their counter-receptors in humans may have severe consequences as exemplified by leukocyte adhesion deficiency (LAD) I or II syndromes. Because such diseases occur with great rarity, animal models are valuable for studying the role of particular adhesion molecules and their natural ligands in immunity. We studied selected immune parameters and general health in mice with a defect in the sialyl-Lewis X antigen (selectin ligand) caused by disruption of the gene encoding alpha(1,3)fucosyltransferase VII (Fuc-TVII). Leukocytes from Fuc-TVII -/- and control mice were tested for adherence to cellophane membranes or polymer particles in vivo and phagocytic activity in vitro. While no difference in adherence was found, the number of neutrophil granulocytes in exudate induced by intraperitoneal injection of polymer beads was reduced in knock-out mice. Moreover, the phagocytic activity in Fuc-TVII -/- mice was significantly reduced. These animals have splenomegaly due to increased hematopoiesis and reduced weight but do not exhibit clinical signs of immunodeficiency. In conclusion, the lack of Fuc-TVII activity leads to several morphological and functional abnormalities without an impact on survival rate.

Deficiency in the glycosyltransferase Gcnt1 increases susceptibility to tuberculosis through a mechanism involving neutrophils

“… 6 , 7 Deficiency in several glycosyltransferases involved in the biosynthesis of functional selectin ligands, as Galnt1 , Gcnt1 , B4galt1 , Fut4 , Fut7 and St3gal4 , results in defective leukocyte recruitment 7 – 9 and in homeostatic alterations, namely pronounced blood neutrophilia. 10 , 11 Selectin ligands are commonly decorated with O -glycans bearing a terminal sialyl Lewis x (sLe x ) (sialic acid α2,3Galβ1–4 (Fucα1,3) GlcNAc-R) epitope. 6 Extensive O -glycosylation is also characteristic of transmembrane or secreted gel-forming mucins, 12 important components of the lung mucus.…”

Fucosylated glycans in the periventricular structures and the cerebrospinal fluid of the fetal rat forebrain. An autoradiographic and lectin binding histiotopic study

“…In addition (iii), fucose residues are also present in the stage spe-cific embryonic antigen-1 (SSEA-1, Le x oligosaccharide) expressed in the proliferation period of the rat and human embryonic brain (Wiederschain et al, 1998;Cailleau-Thomas et al, 2000) in which, as well as in some fast proliferating tumors (Muramatsu and Muramatsu, 1983;Miyoshi et al, 1999), fucosyltransferase and fucosidase genes are also expressed or even up-regulated. Supression of some fucosyltransferase genes in mice in situ caused decreased phagocytic activity of leukocytes (Bartunková et al, 2000). Finally (iv), the germinal zones of the embryonic brain of several species are enriched by fucosylated glycolipids of a not yet determined function (Yamamoto et al, 1985).…”