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

Autor: Thomas Krahn, Roland Kaufmann, Klaus-D Bremm, Ralf Ludwig, Horst Antonicek, Thomas Matthias Zollner, Margarete Schön, Maria-L. Rodriguez, Erwin Bischoff, Kerstin Henninger, Wolf-Henning Boehncke, Matthias Schramm, Christina M. Parker, J. Schultz, Harald Gollnick, Michael P. Schön
Jazyk: angličtina
Rok vydání: 2002
Předmět:
Models
Molecular
Anti-Inflammatory Agents
Non-Steroidal/chemistry/*pharmacology
Transplantation
Heterologous
Heterologous
Oligosaccharides
Cell Movement/drug effects
Mice
SCID
Oligosaccharides/chemistry
Biology
Pharmacology
In Vitro Techniques
General Biochemistry
Genetics and Molecular Biology
Mice
E-Selectin/*drug effects
In vivo
Cell Movement
Psoriasis
Macrolides/chemistry/*pharmacology
medicine
Cell Adhesion
Leukocytes
Animals
Humans
Cell Adhesion/drug effects
Sialyl Lewis X Antigen
Psoriasis/*drug therapy/pathology
Anti-Inflammatory Agents
Non-Steroidal
Leukocytes/*drug effects
General Medicine
Adhesion
Skin Transplantation
medicine.disease
In vitro
Streptomyces
Transplantation
Mice
Inbred C57BL
Immunology
Streptomyces/chemistry
Female
Macrolides
E-Selectin
Selectin
Intravital microscopy
Zdroj: Nature Medicine, Vol. 8, No 4 (2002) pp. 366-372
ISSN: 1078-8956
Popis: 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.
Databáze: OpenAIRE
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