Lessons Learned from Clustering of Fluorinated Glycolipids on Selectin Ligand Function in Cell Rolling
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- 作者：Gabriele Schumacher ; Udo Bakowsky ; Christian Gege ; Richard R. Schmidt ; Ulrich Rothe ; and Gerd Bendas
- 刊名：Biochemistry
- 出版年：2006
- 出版时间：March 7, 2006
- 年：2006
- 卷：45
- 期：9
- 页码：2894 - 2903
- 全文大小：1069K
- 年卷期：v.45,no.9(March 7, 2006)
- ISSN：1520-4995
文摘
Selectin-induced leukocyte rolling along the endothelium is an essential step in the cellularimmune response. Since clustering of binding epitopes is thought to be crucial for selectin-ligandinteraction, we focused on requirements of ligand clusters in a flow chamber study. Neoglycolipids bearingthe binding epitope sialyl Lewis X (sLeX) were used as artificial ligands in model membranes. sLeXligands or matrix lipids or both were applied with partially fluorinated alkyl chains to increase the ligandcluster separation tendency. Cluster size, their inner structure, and separation distance were evaluatedwith high resolution by scanning force microscopy (SFM) and correlated with binding or rolling ofE-selectin-expressing cells. Fluorination of only one component, sLeX ligand or matrix lipid, leads to avery high separation tendency and impeded cell rolling, although firm cell adhesion could be observeddown to 0.005 mol % ligand concentration. As a sign of total immiscibility, cluster size increased withligand concentration, and resulting excessive ligand densities within the clusters prevent cell rolling.Fluorination of both sLeX ligands and matrix created small clusters which could serve as rolling patches.Our results confirmed that cluster size and separation distance controlled by a certain miscibility of ligandand matrix as well as a sufficiently diluted ligand concentration within the clusters are necessary for cellrolling. Within this work, selectin ligand clustering and its ability to mediate cell rolling are presented asa balance between multivalency of binding and sufficient flexibility of the single epitopes. This might behelpful for better understanding the function of the natural selectin ligands.