bimosiamose-disodium and Peritonitis

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.

Topics: Animals; Binding, Competitive; Biphenyl Compounds; E-Selectin; Inflammation; Leukocytes; Ligands; Male; Mannose; Mannosides; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Molecular Mimicry; Neutrophils; P-Selectin; Peptoids; Peritonitis; Thioglycolates; Venules