title: Core2 1-6-N-glucosaminyltransferase-I is crucial for the formation of atherosclerotic lesions in apolipoprotein E-deficient mice.
abstract: OBJECTIVE
  Core2 1-6-N-glucosaminyltransferase-I (C2GlcNAcT-I) modification of adhesion molecules is required for optimal binding to target ligands. The objective of this study was to determine the role of C2GlcNAcT-I in the recruitment of Ly-6C(hi) monocytes to atherosclerotic lesions and in lesion formation in mice.
  
  
  RESULTS
  In a whole-blood binding assay, Ly-6C(hi) monocytes and certain lymphocytes and natural killer cells from wild-type mice bound to P- and E-selectin. C2GlcNAcT-I deficiency abrogated leukocyte binding to P- and E-selectin in this assay as well as in an in vitro flow chamber assay. Moreover, C2GlcNAcT-I deficiency decreased Ly-6C(hi) monocyte interactions with atherosclerotic arteries under physiological flow conditions and also inhibited monocyte recruitment to the peritoneal cavity in mice challenged with thioglycollate. In apolipoprotein E-deficient (apoE(-/-)) mice, lack of C2GlcNAcT-I resulted in fewer and smaller atherosclerotic lesions in mouse aortas. Atherosclerosis was also suppressed in C2GlcNAcT-I(-/-)/apoE(-/-) chimeric mice transplanted with C2GlcNAcT-I(+/+) bone marrow cells.
  
  
  CONCLUSIONS
  C2GlcNAcT-I in both leukocytes and blood vessel wall cells contributes to leukocyte recruitment to the arterial wall. C2GlcNAcT-I deficiency leads to the formation of small, macrophage-poor, and collagen-rich atherosclerotic lesions.
authors.affiliation: Department of Medicine, University of Minnesota, 420 Delaware St SE, MMC508, Minneapolis, MN 55455, USA.
authors.forename: Huan
authors.initials: H
authors.lastname: Wang
authors.forename: Rong
authors.initials: R
authors.lastname: Tang
authors.forename: Weiyu
authors.initials: W
authors.lastname: Zhang
authors.forename: Karine
authors.initials: K
authors.lastname: Amirikian
authors.forename: Zhen
authors.initials: Z
authors.lastname: Geng
authors.forename: Jianguo
authors.initials: J
authors.lastname: Geng
authors.forename: Robert P
authors.initials: RP
authors.lastname: Hebbel
authors.forename: Lijun
authors.initials: L
authors.lastname: Xia
authors.forename: Jamey D
authors.initials: JD
authors.lastname: Marth
authors.forename: Minoru
authors.initials: M
authors.lastname: Fukuda
authors.forename: Shigeki
authors.initials: S
authors.lastname: Katoh
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Huo
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000201:enzymology* / Q000209:etiology / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D001854:Bone Marrow Cells / Q000201:enzymology / Q000276:immunology; D016026:Bone Marrow Transplantation; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte; D004036:Diet, Atherogenic; D004195:Disease Models, Animal; D019040:E-Selectin / Q000378:metabolism; D005260:Female; D007249:Inflammation / Q000201:enzymology / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D017351:N-Acetylglucosaminyltransferases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D019007:P-Selectin / Q000378:metabolism; D011673:Pulsatile Flow; D013997:Time Factors; D018183:Transplantation Chimera
chemical_list: D000950:Antigens, Ly; D001057:Apolipoproteins E; D019040:E-Selectin; C494192:Ly-6C antigen, mouse; D019007:P-Selectin; D017351:N-Acetylglucosaminyltransferases; C053024:beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,6-acetylglucosaminyl transferase