Premium
The anti‐inflammatory effects of a selectin ligand mimetic, TBC‐1269, are not a result of competitive inhibition of leukocyte rolling in vivo
Author(s) -
Hicks Anne E. R.,
Abbitt Kate B.,
Dodd Paul,
Ridger Victoria C.,
Hellewell Paul G.,
Norman Keith E.
Publication year - 2005
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.1103573
Subject(s) - in vivo , selectin , in vitro , immunology , inflammation , biology , l selectin , peritonitis , cell adhesion molecule , biochemistry , genetics , microbiology and biotechnology
Selectins and their ligands support leuocyte rolling, facilitating the subsequent firm adhesion and migration that occur during inflammation. TBC‐1269 (Bimosiamose), a structural mimetic of natural selectin ligands, inhibits P‐, E‐, and L‐selectin in vitro, has anti‐inflammatory effects in vivo, and recently underwent phase II clinical trials for childhood asthma and psoriasis. We studied whether the anti‐inflammatory effects of TBC‐1269 could be related to leukocyte rolling in vivo. Although TBC‐1269 inhibited rolling of a murine leukocyte cell line on murine P‐selectin in vitro and thioglycollate‐induced peritonitis in vivo, it did not alter leukocyte rolling in mouse cremaster venules. TBC‐1269 reduced neutrophil recruitment in thioglycollate‐induced peritonitis in wild‐type and P‐selectin−/− mice but not in E‐selectin−/− mice. We suggest that the in vivo effects of TBC‐1269 may be mediated through E‐selectin but do not appear to involve leukocyte rolling.