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Therapeutic potential of a novel synthetic selectin blocker, OJ‐R9188, in allergic dermatitis
Author(s) -
IkegamiKuzuhara Akemi,
Yoshinaka Tsuyoshi,
Ohmoto Hiroshi,
Inoue Yoshimasa,
Saito Tadayuki
Publication year - 2001
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0704397
Subject(s) - selectin , in vivo , chemistry , in vitro , pharmacology , sialyl lewis x , extravasation , peritoneal cavity , immunology , biochemistry , microbiology and biotechnology , medicine , inflammation , biology , anatomy
We investigated the ability of a newly synthesized sugar derivative, OJ‐R9188, {N‐(2‐tetradecylhexadecanoyl)‐O‐( L ‐alpha‐fucofuranosyl)‐ D ‐seryl}‐ L ‐glutamic acid 1‐methylamide 5‐ L ‐arginine salt, to block binding of selectins to their ligands in vitro and inhibit the infiltration of leukocytes in vivo . OJ‐R9188 prevented the binding of human E‐, P‐ and L‐selectin‐IgG fusion proteins to immobilized sialyl Lewis x (sLe x )‐pentasaccharide glycolipid, with IC 50 values of 4.3, 1.3, and 1.2 μ M , respectively. In a mouse model of thioglycollate‐induced peritonitis, OJ‐R9188 at 10 mg kg −1 , i.v. inhibited neutrophil accumulation in the peritoneal cavity. In the IgE‐mediated skin reaction, OJ‐R9188 at 3 and 10 mg kg −1 , i.v. significantly inhibited extravasation of neutrophils and eosinophils into the inflammatory sites and at 10 mg kg −1 , i.v. also inhibited infiltration caused by picryl chloride‐induced delayed‐type hypersensitivity in mice. These results suggest that OJ‐R9188 may be a useful selectin blocker, with activity against human and mouse E‐, P‐ and L‐selectins in vitro and in vivo , and that blocking selectin‐sLe x binding is a promising strategy for the treatment of allergic skin diseases.British Journal of Pharmacology (2001) 134 , 1498–1504; doi: 10.1038/sj.bjp.0704397