Dendritic polyglycerol sulfates as multivalent inhibitors of inflammation

• DOI: 10.1073/pnas.1003103107
• Publication Date: 2010-11-02T05:22:00Z
• Authors: Jens Dernedde; Alexandra Rausch; Marie Weinhart; Sven Enders; Rudolf Tauber; Kai Licha; Michael Schirner; Ulrich Zügel; Arne von Bonin; Rainer Haag
• Keywords: Leukocyte extravasation; Extravasation

Adhesive interactions of leukocytes and endothelial cells initiate leukocyte migration to inflamed tissue are important for immune surveillance. Acute chronic inflammatory diseases show a dysregulated response result in massive efflux that contributes further damage. Therefore, targeting trafficking may provide potent form anti-inflammatory therapy. Leukocyte is initiated by the cell adhesion molecules E-, L-, P-selectin their corresponding carbohydrate ligands. Compounds efficiently address these therefore high therapeutic interest. Based on this rationale we investigated synthetic dendritic polyglycerol sulfates (dPGS) as macromolecular inhibitors operate via multivalent binding mechanism mimicking naturally occurring dPGS inhibited both leukocytic L-selectin with efficacy. Size degree sulfation polymer core determined selectin affinity. Administration contact dermatitis mouse model dampened extravasation effectively glucocorticoids did edema formation was significantly reduced. In addition, interacted complement factors C3 C5 shown vitro reduced C5a levels activation. Thus, represent an innovative class fully therapeutics be used treatment diseases.