Synthesis of {alpha}(1,3) fucosyltransferases IV- and VII-dependent eosinophil selectin ligand and recruitment to the skin.
Selectins mediate the initial adhesion of leukocytes to endothelial cells in many contexts of inflammation-dependent leukocyte recruitment. The glycans that contribute to P- and E-selectin counterreceptor activity arise through glycosylation reactions in which the terminal steps are catalyzed by alpha(1,3) fucosyltransferases (FTs). We examined how selectin ligand activities are controlled in eosinophils by characterizing FT expression profiles and regulatory mechanisms in eosinophils isolated from human blood. We found that FT-IV and FT-VII mRNAs were up-regulated by transforming growth factor-beta1, but the FT-IV transcript consistently predominated in eosinophils. To further define the physiological role of FT-IV and FT-VII in expression of eosinophil selectin ligand, we characterized models of dermal eosinophilia in FT-IV- and/or FT-VII-deficient mice in vivo. FT-IV deficiency yielded a significant decrease in eosinophil recruitment to the skin. Likewise, deficiency of FT-VII also yielded a decrease in eosinophil recruitment. Eosinophil recruitment that remained in the absence of FT-VII was further inhibited by blocking P- or E-selectin and was essentially absent in mice deficient in both enzymes. These observations indicate that FT-IV and FT-VII are both important contributors to selectin-dependent eosinophil recruitment to the skin and may represent therapeutic targets for treating diseases in which eosinophil recruitment contributes to pathophysiology.
Satoh
Takahiro
T
Department of Dermatology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan. tasa-1688.derm@tmd.ac.jp
Kanai
Yasumasa
Y
Wu
Ming-Hua
MH
Yokozeki
Hiroo
H
Kannagi
Reiji
R
Lowe
John B
JB
Nishioka
Kiyoshi
K
D000818:Animals; D001773:Blood Cells / Q000378:metabolism; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000494:pharmacology; D003872:Dermatitis / Q000209:etiology; D019040:E-Selectin / Q000378:metabolism; D004802:Eosinophilia / Q000139:chemically induced / Q000209:etiology*; D004804:Eosinophils / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005647:Fucosyltransferases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016256:Lewis X Antigen; D008024:Ligands; D051379:Mice; D018345:Mice, Knockout; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics; D019007:P-Selectin / Q000378:metabolism; D012333:RNA, Messenger / Q000097:blood / Q000378:metabolism; D019087:Selectins / Q000378:metabolism*; D012867:Skin / Q000187:drug effects; D012871:Skin Diseases / Q000139:chemically induced / Q000209:etiology* / Q000473:pathology
C515456:CCL11 protein, human; C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D019742:Chemokines, CC; D019040:E-Selectin; D016256:Lewis X Antigen; D008024:Ligands; D019007:P-Selectin; D012333:RNA, Messenger; D019087:Selectins; C066693:FUT4 protein, human; C502597:FUT7 protein, human; D005647:Fucosyltransferases; D017351:N-Acetylglucosaminyltransferases; C053024:beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,6-acetylglucosaminyl transferase