Einfluss der Chemokinpräsentation auf das Reaktionsmuster von Leukozyten

趋化因子呈递对白细胞反应模式的影响

• 批准号: 159587272
• 负责人: Professor Michael Sixt
• 金额: --
• 依托单位: Institute of Science and Technology Austria
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2009
• 资助国家: 德国
• 起止时间: 2008-12-31 至 2012-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/159587272?language=en
• 关键词: Einfluss; der; Chemokinpr; sentation; auf

Chemokines orchestrate immune cell trafficking by inducing either directed or random migration and by activating integrins in order to support adhesion to surfaces. Our preliminary data suggest that the way how chemokines are presented within lymphatic organs determines these different responses. The chemokine receptor CCR7 that is expressed on naive T cells and activated dendritic cells has two ligands: CCL19 and CCL2I, which differ in their ability to bind heparan sulfates. We found that the surface immobilized form of the heparan sulfate anchoring CCL2I caused random movement of dendritic cells that was confmed to the solid phase field by integrin mediated adhesion. Upon direct coniact with CCL21, dendritic cells proteolytically created a solubilized variant of CCL2I that formed a diffusion gradient. This fluid phase gradient triggered tactic movement but not integrin activation allowing the cells to move independent of surface adhesion. This reactivity pattem resembled CCL 19 that is not proteolytically processed. We want to address the molecular mechanisms ofthis proteolytic processing as well as its consequences for leukocyte trafficking within skin and lymph node.

趋化因子通过诱导定向或随机迁移以及通过活化整联蛋白来协调免疫细胞运输，以支持对表面的粘附。我们的初步数据表明，趋化因子在淋巴器官内的呈现方式决定了这些不同的反应。在初始T细胞和活化的树突状细胞上表达的趋化因子受体CCR7具有两种配体：CCL19和CCL2I，其结合硫酸乙酰肝素的能力不同。我们发现，表面固定形式的硫酸乙酰肝素锚定CCL 2I引起随机运动的树突状细胞，这是confmed的固相领域的整合素介导的粘附。在与CCL21直接接触时，树突状细胞蛋白水解产生CCL2I的溶解变体，其形成扩散梯度。这种流体相梯度触发了战术运动，但没有整合素激活，使细胞移动独立于表面粘附。这种反应模式类似于未经蛋白水解处理的CCL 19。我们希望阐明这种蛋白水解过程的分子机制及其对皮肤和淋巴结内白细胞运输的影响。