Details

Autor(en) / Beteiligte

• Tavernaro, Isabella
• Rodrigo, Alberto Marti
• Kandziora, Maja
• Kuntz, Sabine
• Dernedde, Jens
• Trautwein, Christian
• Tacke, Frank
• Blas‐Garcia, Ana
• Bartneck, Matthias

Titel

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

Ist Teil von

• Advanced therapeutics, 2019-12, Vol.2 (12), p.n/a

Erscheinungsjahr

2019

Link zum Volltext

Quelle

Wiley-Blackwell Full Collection

Beschreibungen/Notizen

• 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. In order to study the impact of different sulfated and non‐sulfated carbohydrate mimetics on leukocyte functionality, a library of nanospheres made of different materials and equipped with various bioactive ligands is systematically designed. The importance of ligand sulfation, L‐selectin binding, and the degree of valency for controlling immune cell motility is outlined.