Efomycine M, a new specific inhibitor of selectin, impairs leukocyte adhesion and alleviates cutaneous inflammation.
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| Abstract |
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.
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| Authors | Michael P Schön, Thomas Krahn, Margarete Schön, Maria-L Rodriguez, Horst Antonicek, Jeanette E Schultz, Ralf J Ludwig, Thomas M Zollner, Erwin Bischoff, Klaus-D Bremm, Matthias Schramm, Kerstin Henninger, Roland Kaufmann, Harald P M Gollnick, Christina M Parker, W-Henning Boehncke |
| Journal | Nature medicine (Nat Med) Vol. 8 Issue 4 Pg. 366-72 (Apr 2002) ISSN: 1078-8956 [Print] United States |
| PMID | 11927942 (Publication Type: Journal Article) |
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