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Modulating Myeloid Immune Cell Migration Using Multivalently Presented Monosaccharide Ligands for Advanced Immunotherapy

  • Abstract Due to their importance for the outcome of the inflammatory response, the motile myeloid cells are a focus of novel treatment options. The interplay of selectins and their ligands with leukocytes and endothelial cells, which mediate endothelial attachment and transmigration of immune cells, can be modulated by selectin-binding structures. Here, a library of selectin-targeting ligands coupled to either gold, silver, iron oxide nanospheres, or quantum dots of 5–10 nm in size is used to systematically study their impact on immune cell motility. The multivalent presentation of the carbohydrate mimetics results in very low sub-nanomolar binding to L-selectin. Using human primary monocytes, granulocytes, lymphocytes, and macrophages, it is shown that the ligands exhibit only minor effects on uptake, whereas the motility of leukocytes is critically affected as observed in migration assays evaluated by flow cytometry. The carbohydrate mimetic ring structure, sulfation, in particular, and the degree of ligand presentation, are constituents which cohere in this process. Specific carbohydrate ligands can thus selectively regulate leukocyte subsets. These data form the basis for advanced immunotherapy which inhibits the amplification of inflammation by restricting leukocyte influx to injured tissue sites. Furthermore, the targeting ligands may complement existing treatment options for inflammatory diseases.

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Document Type:Article
Author:Isabella Tavernaro, Alberto Marti Rodrigo, Maja Kandziora, Sabine Kuntz, Jens Dernedde, Christian Trautwein, Frank Tacke, Ana Blas-Garcia, Matthias Bartneck
Parent Title (English):Advanced Therapeutics
First Page:1900145
Year of first Publication:2019
Release Date:2022/11/18
Impact:12.441 (2019)
Funding Information:Wilhelm Sander-Stiftung. Grant Number: 2018.129.1 European Molecular Biology Organization. Grant Number: 7033; European Cooperation in Science and Technology. Grant Number: BM1404; DFG
Groups:Nano Zell Interaktionen
Open Access:Open Access
Signature:INM 2019/107
Licence (German):License LogoCreative Commons - CC BY-NC-ND - Namensnennung - Nicht kommerziell - Keine Bearbeitungen 4.0 International