Journal of Leukocyte Biology Myeloid cells, immune suppression, tumor immunology
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Originally published online as doi:10.1189/jlb.1103573 on October 5, 2004

Published online before print October 5, 2004
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(Journal of Leukocyte Biology. 2005;77:59-66.)
© 2005 by Society for Leukocyte Biology

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. Norman1

Cardiovascular Research Unit, University of Sheffield, United Kingdom

1 Correspondence: University of Sheffield, Clinical Sciences Centre, Northern General Hospital, Herries Road, Sheffield S5 7AU, UK. E-mail: k.norman{at}sheffield.ac.uk

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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