en
Scientific article
English

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

Published inJournal of investigative dermatology, vol. 129, no. 5, p. 1192-1202
Publication date2009
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
Affiliation Not a UNIGE publication
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
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ISSN of the journal0022-202X
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