PS3, A semisynthetic Β-1,3-glucan sulfate, diminishes contact hypersensitivity responses through inhibition of L- and P-selectin functions

Susanne Alban, Ralf J. Ludwig, Gerd Bendas, Michael P. Schön, Gertie J. Oostingh, Heinfried H. Radeke, Juliane Fritzsche, Josef Pfeilschifter, Roland Kaufmann, Wolf Henning Boehncke

26 Citations (Scopus)

Abstract

Leukocyte extravasation is initiated by an interaction of selectin adhesion molecules and appropriate carbohydrate ligands. Targeting those interactions seems a promising approach to treat chronic inflammation. We developed a Β-1, 3-glucan sulfate (PS3) with inhibitory activity toward L and P-selectins under static conditions. Here, detailed investigation showed inhibition of P- and L-selectins, but not E-selectin under flow conditions (relative reduction of interaction with appropriate ligands to 34.4±16.6, 8.5±3.6, or 99.5±9.9%, respectively, by PS3 for P-, L- or E-selectin). Intravital microscopy revealed reduction of leukocyte rolling in skin microvasculature from 22.7±5.0 to 12.6±4.0% after injection of PS3. In the next experiments, mice were sensitized with 2,4,- dinitrofluorobenzene (DNFB), and lymphocytes were transferred into syngeneic recipients, which were challenged by DNFB. Inflammatory responses were reduced when immunity was generated in mice treated with PS3 or in L-selectin-deficient mice. No effect was observed when L-selectin-deficient donor mice were treated with PS3, further suggesting that PS3 acted primarily through inhibition of L-selectin. Elicitation of a contact hypersensitivity response was reduced in P-selectin-deficient and in PS3-treated mice. Again, PS3 had no effect in P-selectin-deficient mice. PS3 is a potent P- and L-selectin inhibitor that may add to the therapy of inflammatory diseases.

Original languageEnglish
JournalJournal of Investigative Dermatology
Volume129
Issue number5
Pages (from-to)1192-1202
Number of pages11
ISSN0022-202X
DOIs
Publication statusPublished - 01.05.2009

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