Fucosyltransferases: structure/function studies

Vries, Theodora de; Knegtel, Ronald M.A.; Holmes, Eric H.; Macher, Bruce A.

doi:10.1093/glycob/11.10.119r

Cited by 176 publications

(113 citation statements)

References 71 publications

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“…Among six ␣1,3-FucT responsible for synthesis of sLe x , we examined the expression of FucT-III, -IV, -VII, and -IX in two bronchial epithelial cell lines (1HAEo Ϫ and 16HBE 14o Ϫ ) and primary cells. FucT-V and -VI do not appear to have an essential biological role, and not all humans have functional forms of these enzymes (8). We found that FucT-IV is the only gene expressed in all airway epithelial cells examined (Table 1); therefore, FucT-IV is to be considered the main FucT in the study of airway epithelial repair.…”

Section: Fig 4 Blocking Of Slementioning

confidence: 80%

Airway epithelial wound repair: role of carbohydrate sialyl Lewis^x

Allahverdian¹,

Wojcik²,

Dorscheid³

2006

American Journal of Physiology-Lung Cellular and Molecular Phys

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Epithelial repair is a complex cellular and molecular process, the details of which are still not clearly understood. Plasma membrane glycoconjugates can modulate cell function by altering the function of protein and lipids. Sialyl Lewisx(sLex), a fucose-containing tetrasaccharide, decorates membrane-bound and secreted proteins and mediates cell-cell interaction. In the present study we investigated the role of sLexin airway epithelial repair. Using immunohistochemistry, we showed an increased expression of sLexin areas of damaged bronchial epithelium compared with intact regions. Confluent monolayers of airway epithelial cells were mechanically wounded and allowed to close. Wounded monolayers were photographed for wound closure kinetics, fixed for immunocytochemical studies, or subjected to RNA extraction. Examining the expression of different α1,3-fucosyltransferases (FucT), enzymes that mediate the final step in the synthesis of sLex, we found that FucT-IV was the common gene expressed in all cell lines and primary airway epithelial cells. We demonstrated an increased expression of sLexover time after mechanical injury. Blocking of sLexwith an inhibitory antibody completely prevented epithelial repair. Our data suggest an essential functional role for sLexin epithelial repair. Further studies are necessary to explore the exact mechanism for sLexin mediating cell-cell interaction in bronchial epithelial cells to facilitate epithelial migration and repair.

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Section: Fig 4 Blocking Of Slementioning

confidence: 80%

Airway epithelial wound repair: role of carbohydrate sialyl Lewis^x

Allahverdian¹,

Wojcik²,

Dorscheid³

2006

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…The fucosyltransferase gene family encodes enzymes that transfer fucose in a1,2, a1,3/4, and a1,6 linkages on a large variety of glycans (Huang et al 2000, Wagers & Kansas 2000, Withers & Hakomori 2000, de Vries et al 2001. FUT4 belongs to a subfamily of a1/3/4 fucosyltransferases.…”

Section: Introductionmentioning

confidence: 99%

Expression and regulation of fucosyltransferase 4 in human endometrium

Ponnampalam¹,

Rogers²

2008

Reproduction

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It has been suggested that selectin ligands expressed by the endometrial epithelium are essential for the initial adhesion of the blastocyst to the luminal epithelium of human endometrium. One of the enzymes responsible for the production of selectin ligands is fucosyltransferase 4 (FUT4), a member of a1,3 fucosyltransferases. The aims of the present study were to characterize FUT4 mRNA and protein in human endometrium during the menstrual cycle and to investigate the hormonal regulation of FUT4 whose mRNA expression was quantified by real-time PCR in fresh endometrial tissue from cycling women and protein expression was analyzed by immunohistochemistry and Western blotting. Hormonal regulation of FUT4 transcription was investigated using an endometrial explant system. FUT4 mRNA was significantly upregulated in fresh tissues during early and mid-secretory phases when compared with other phases of the menstrual cycle. FUT4 protein was localized to glandular and luminal epithelium and the expression levels followed the same pattern as for FUT4 mRNA. Our data also show that, in proliferative explants, progesterone significantly increased FUT4 transcription and translation after 24 h in culture. The inductive effect of progesterone on FUT4 transcription was lost after 48 h of treatment. Estrogen did not have any significant effects. These data suggest that the upregulation of selectin ligands in the human endometrium at the time of implantation may be mediated, at least in part, by the regulation of FUT4 expression.

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“…Because the expression of FUT genes is tissue-and cell-type dependent 23 and FUT2 expression is much lower than FUT1 in HUVECs, 22 it is expectable that there was no significant change of FUT2 mRNA levels in TNF-α-activated HUVECs.…”

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confidence: 99%

Recombinant Lectin-Like Domain of Thrombomodulin Suppresses Vascular Inflammation by Reducing Leukocyte Recruitment via Interacting With Lewis Y on Endothelial Cells

Lin

Chang

Shi

et al. 2013

ATVB

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Lin et al TM Lectin-Like Domain and Le y in Inflammation 2367recombinant TMD1 (rTMD1) has been shown to attenuate inflammation by inhibiting complement activation 8 and sequestering high mobility group box B1 protein. 9 However, except for high mobility group box B1, other interacting molecules of TMD1 that may participate in anti-inflammation are still unknown.Previously, we demonstrated that Lewis Y (Le y ; Fucα1-2Galβ1-4(Fucα1-3)GlcNAcβ1-R) is a specific carbohydrate ligand of rTMD1. 10,11 Le y is known to be highly expressed in epithelial cells, especially in cancer tissues, 12 where Le y mediates cell adhesion, 13,14 proliferation, 15,16 and apoptosis. 13,17,18 Meanwhile, recent studies have demonstrated that Le y is upregulated in synovial endothelium and joint fluid in rheumatoid arthritis. 19,20 Le y is also found to be expressed on intercellular adhesion molecule-2 (ICAM-2) on endothelial cells. ICAM-2 is a ligand of dendritic cell-specific C-type lectin, dendritic cell-specific ICAM-3-grabbing nonintegrin. The interaction of dendritic cell-specific ICAM-3-grabbing nonintegrin with ICAM-2 on vascular endothelium is Le y dependent and is essential for dendritic cell-specific ICAM-3-grabbing nonintegrin recruitment into tissues to mediate immune responses. 21,22 These findings suggest that interaction of Le y with lectin-containing receptor might be involved in recruitment of leukocytes in inflammatory responses. Because Le y is a specific ligand of rTMD1, we hypothesize that rTMD1/ Le y interaction on endothelial cells would influence leukocyte recruitment, thereby suppressing inflammation.To test our hypothesis, we examined the expression and function of Le y in endothelial cells under inflammatory conditions and studied the effect of rTMD1/Le y binding on anti-inflammation in vitro and in vivo. We discovered that leukocyte recruitment was interfered by rTMD1/Le y interaction. Animal inflammation models of thioglycollate-induced peritonitis, carotid ligation injury, and atherosclerosis were applied to further evidence the protective effect of rTMD1. On the basis of these findings, we provide a novel mechanism that rTMD1 decreases leukocyte recruitment by binding to Le y and may further attenuate inflammatory responses. Materials and MethodsMaterials and Methods are available in the online-only Supplement. Results Le y Mediates Leukocyte Adhesion on InflammationTo investigate the role of Le y in inflammation, we initially tested whether Le y expression in endothelial cells would be induced by stimulation of the proinflammatory cytokine, tumor necrosis factor-α (TNF-α). As shown in Figure 1A, mRNA levels of fucosyltransferase 1 (FUT)1, FUT2, and FUT4 for Le y synthesis 23 in endothelial cells were measured. The expression of FUT4 and FUT1 was significantly increased after TNF-α stimulation for 12 and 24 hours, respectively; meanwhile, no significant difference was found in the expression of FUT2. In addition, higher Le y expression on the surface of endothelial cells was observed using flow cytometry and...

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Fucosyltransferases: structure/function studies

Cited by 176 publications

References 71 publications

Airway epithelial wound repair: role of carbohydrate sialyl Lewis^x

Airway epithelial wound repair: role of carbohydrate sialyl Lewis^x

Expression and regulation of fucosyltransferase 4 in human endometrium

Recombinant Lectin-Like Domain of Thrombomodulin Suppresses Vascular Inflammation by Reducing Leukocyte Recruitment via Interacting With Lewis Y on Endothelial Cells

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Fucosyltransferases: structure/function studies

Cited by 176 publications

References 71 publications

Airway epithelial wound repair: role of carbohydrate sialyl Lewisx

Airway epithelial wound repair: role of carbohydrate sialyl Lewisx

Expression and regulation of fucosyltransferase 4 in human endometrium

Recombinant Lectin-Like Domain of Thrombomodulin Suppresses Vascular Inflammation by Reducing Leukocyte Recruitment via Interacting With Lewis Y on Endothelial Cells

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Airway epithelial wound repair: role of carbohydrate sialyl Lewis^x

Airway epithelial wound repair: role of carbohydrate sialyl Lewis^x