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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.1103573

Received for publication November 19, 2003.
Revised August 13, 2004.
Accepted for publication September 14, 2004.

Article

The anti-inflammatory effects of a selectin ligand mimetic, TBC-1269, are not a result of competitive inhibition of leukocyte rolling in vivo

Anne E. R. Hicks , Kate B. Abbitt , Paul Dodd , Victoria C. Ridger , Paul G. Hellewell , and Keith E. Norman @

Cardiovascular Research Unit, University of Sheffield, United Kingdom

@ To whom correspondence should be addressed. E-mail: k.norman{at}sheffield.ac.uk.


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Abstract

Selectins and their ligands support leukocyte 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.

Key Words: inflammation • neutrophils • in vivo animal models • intravital microscopy • venules • sialyl LewisX • flow-based adhesion assay




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