There is an Erratum (June 2002) associated with this Article.
Efomycine M, a new specific inhibitor of selectin, impairs leukocyte adhesion and alleviates cutaneous inflammation
Michael P. Schön1, Thomas Krahn2, Margarete Schön1, Maria-L. Rodriguez3, Horst Antonicek3, Jeanette E. Schultz4, Ralf J. Ludwig4, Thomas M. Zollner4, Erwin Bischoff2, Klaus-D. Bremm2, Matthias Schramm2, Kerstin Henninger2, Roland Kaufmann4, Harald P. M. Gollnick1, Christina M. Parker5
& W.-Henning Boehncke4
1
Department of Dermatology, Otto-von-Guericke-University, Magdeburg, Germany
Specific interference with molecular mechanisms guiding tissue localization of leukocytes may be of great utility for selective immunosuppressive therapies. We have discovered and characterized efomycines, a new family of selective small-molecule inhibitors of selectin functions. Members of this family significantly inhibited leukocyte adhesion in vitro. Efomycine M, which was nontoxic and showed the most selective inhibitory effects on selectin-mediated leukocyte-endothelial adhesion in vitro, significantly diminished rolling in mouse ear venules in vivo as seen by intravital microscopy. In addition, efomycine M alleviated cutaneous inflammation in two complementary mouse models of psoriasis, one of the most common chronic inflammatory skin disorders. Molecular modeling demonstrated a spatial conformation of efomycines mimicking naturally occurring selectin ligands. Efomycine M might be efficacious in the treatment of human inflammatory disorders through a similar mechanism.
