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.; Kaufmann, Roland; Boehncke, Wolf-Henning

doi:10.1038/jid.2008.358

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Title		PS3, a semisynthetic beta-1,3-glucan sulfate, diminishes contact hypersensitivity responses through inhibition of L- and P-selectin functions
Authors		Alban, Susanne Ludwig, Ralf J. Bendas, Gerd Schon, Michael P. Oostingh, Gertie J. Radeke, Heinfried H. Fritzsche, Juliane Pfeilschifter, Josef M. Kaufmann, Roland Boehncke, Wolf-Henning show all authors [1 - 10]
Published in		The 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 Transfer — Allergens/immunology/pharmacology — Animals — Cell Communication/drug effects — Cells, Cultured — Dermatitis, Contact/drug therapy/immunology/metabolism — Dinitrofluorobenzene/immunology/pharmacology — Disease Models, Animal — Endothelium, Vascular/cytology/drug effects — Glucans/pharmacology/therapeutic use — Humans — L-Selectin/drug effects/metabolism — Leukocytes, Mononuclear/cytology/drug effects — Male — Mice — Mice, Inbred C57BL — P-Selectin/*drug effects/metabolism — Beta-Glucans/pharmacology/therapeutic use
Identifiers		DOI: 10.1038/jid.2008.358 PMID: 19052560
Full text		Article - Limited access to UNIGE Other version: http://www.nature.com/jid/journal/v129/n5/pdf/jid2008358a.pdf
Citation (ISO format)		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 https://archive-ouverte.unige.ch/unige:29757