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

Alban, Susanne
Ludwig, Ralf J.
Bendas, Gerd
Schon, Michael P.
Oostingh, Gertie J.
Radeke, Heinfried H.
Fritzsche, Juliane
Pfeilschifter, Josef M.
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Published in Journal of investigative dermatology. 2009, vol. 129, no. 5, p. 1192-1202
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 beta-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.
Keywords Adoptive TransferAllergens/immunology/pharmacologyAnimalsCell Communication/drug effectsCells, CulturedDermatitis, Contact/*drug therapy/*immunology/metabolismDinitrofluorobenzene/immunology/pharmacologyDisease Models, AnimalEndothelium, Vascular/cytology/drug effectsGlucans/*pharmacology/therapeutic useHumansL-Selectin/*drug effects/metabolismLeukocytes, Mononuclear/cytology/drug effectsMaleMiceMice, Inbred C57BLP-Selectin/*drug effects/metabolismBeta-Glucans/pharmacology/therapeutic use
PMID: 19052560
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ALBAN, Susanne et al. PS3, a semisynthetic beta-1,3-glucan sulfate, diminishes contact hypersensitivity responses through inhibition of L- and P-selectin functions. In: Journal of investigative dermatology, 2009, vol. 129, n° 5, p. 1192-1202. doi: 10.1038/jid.2008.358

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Deposited on : 2013-09-20

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