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

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.

• Authors: Anne E R Hicks, Kate B Abbitt, Paul Dodd, Victoria C Ridger, Paul G Hellewell, Keith E Norman
• Journal: Journal of leukocyte biology (J Leukoc Biol) Vol. 77 Issue 1 Pg. 59-66 (Jan 2005) ISSN: 0741-5400 [Print] United States
• PMID: 15466915 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biphenyl Compounds
• E-Selectin
• Ligands
• Mannosides
• P-Selectin
• Peptoids
• Thioglycolates
• bimosiamose disodium
• Mannose

Topics

• Animals
• Binding, Competitive
• Biphenyl Compounds (therapeutic use)
• E-Selectin (genetics, immunology, physiology)
• Inflammation (pathology)
• Leukocytes (immunology, metabolism, pathology)
• Ligands
• Male
• Mannose (analogs & derivatives)
• Mannosides (therapeutic use)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Knockout
• Molecular Mimicry
• Neutrophils (immunology, metabolism, pathology)
• P-Selectin (genetics, immunology, physiology)
• Peptoids (chemistry, pharmacology)
• Peritonitis (chemically induced, pathology)
• Thioglycolates (toxicity)
• Venules (cytology)