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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 language | English |
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Journal | Journal of Investigative Dermatology |
Volume | 129 |
Issue number | 5 |
Pages (from-to) | 1192-1202 |
Number of pages | 11 |
ISSN | 0022-202X |
DOIs | |
Publication status | Published - 01.05.2009 |
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Dive into the research topics of 'PS3, A semisynthetic Β-1,3-glucan sulfate, diminishes contact hypersensitivity responses through inhibition of L- and P-selectin functions'. Together they form a unique fingerprint.Projects
- 1 Finished
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Contribution of junctional adhesion molecule (JAM)-B to the distinct steps of lymphocyte extravasation
Ludwig, R. (Principal Investigator (PI))
01.01.06 → 31.12.09
Project: DFG Projects › DFG Individual Projects