Barmore Austin J, Castex Sally M, Gouletas Brittany A, Griffith Alex J, Metz Slater W, Muelder Nicolas G, Populin Michael J, Sackett David M, Schuster Abigail M, Veldkamp Christopher T
Department of Chemistry, University of Wisconsin-Whitewater, 800 West Main Street, Whitewater, WI 53190, USA.
Department of Chemistry, University of Wisconsin-Whitewater, 800 West Main Street, Whitewater, WI 53190, USA; Department of Biochemistry, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
Biochem Biophys Res Commun. 2016 Sep 2;477(4):602-606. doi: 10.1016/j.bbrc.2016.06.098. Epub 2016 Jun 21.
Chemokines direct the migration of cells during various immune processes and are involved in many disease states. For example, CCL19 and CCL21, through activation of the CCR7 receptor, recruit dendritic cells and naïve T-cells to the secondary lymphoid organs aiding in balancing immune response and tolerance. However, CCL19 and CCL21 can also direct the metastasis of CCR7 expressing cancers. Chemokine binding to glycosaminoglycans, such as heparin, is as important to chemokine function as receptor activation. CCL21 is unique in that it contains an extended C-terminus not found in other chemokines like CCL19. Deletion of this extended C-terminus reduces CCL21's affinity for heparin and transferring the CCL21 C-terminus to CCL19 enhances heparin binding mainly through non-specific, electrostatic interactions.
趋化因子在各种免疫过程中指导细胞迁移，并参与多种疾病状态。例如，CCL19和CCL21通过激活CCR7受体，将树突状细胞和初始T细胞募集到次级淋巴器官，有助于平衡免疫反应和耐受性。然而，CCL19和CCL21也可以指导表达CCR7的癌症的转移。趋化因子与糖胺聚糖（如肝素）的结合对趋化因子功能与受体激活同样重要。CCL21的独特之处在于它含有一个在其他趋化因子（如CCL19）中未发现的延伸C末端。删除这个延伸的C末端会降低CCL21对肝素的亲和力，而将CCL21的C末端转移到CCL19上则主要通过非特异性静电相互作用增强肝素结合。
