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Scientific article
English

Efomycine M, a new specific inhibitor of selectin, impairs leukocyte adhesion and alleviates cutaneous inflammation

Published inNature medicine, vol. 8, no. 4, p. 366-372
Publication date2002
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.

Keywords
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal/chemistry/*pharmacology
  • Cell Adhesion/drug effects
  • Cell Movement/drug effects
  • E-Selectin/*drug effects
  • Female
  • Humans
  • Leukocytes/*drug effects
  • Macrolides/chemistry/*pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Mice, SCID
  • Models, Molecular
  • Oligosaccharides/chemistry
  • Psoriasis/*drug therapy/pathology
  • Skin Transplantation
  • Streptomyces/chemistry
  • Transplantation, Heterologous
Affiliation Not a UNIGE publication
Citation (ISO format)
SCHON, Michael P. et al. Efomycine M, a new specific inhibitor of selectin, impairs leukocyte adhesion and alleviates cutaneous inflammation. In: Nature medicine, 2002, vol. 8, n° 4, p. 366–372. doi: 10.1038/nm0402-366
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ISSN of the journal1078-8956
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