Low-molecular-weight heparins inhibit CCL21-induced T cell adhesion and migration
Low-molecular-weight heparins inhibit CCL21-induced T cell adhesion and migration
复制标题
DOI：
10.1124/jpet.302.1.290
复制
发表时间：
2002-07-01
影响因子：
3.5
通讯作者：
Hromas, RA
中科院分区：
文献类型：
--
作者：
Christopherson, KW;Campbell, JJ;Hromas, RA
趋化因子CCL 21，也称为Exodus-2/6-Ckine/次级淋巴组织趋化因子/T细胞激活蛋白-4，是迄今为止描述的最有效的T细胞迁移和粘附刺激剂。内皮肝素样糖胺聚糖（GAG）被认为在炎症部位呈递趋化因子，维持白细胞可以响应的局部浓度梯度。相反，本研究发现GAG显著抑制CCL 21刺激T细胞粘附和趋化的能力。酶，如肝素酶，分裂糖胺聚糖成硫酸化的β-氨基糖苷酶消除这种抑制作用，表明局部组织调节CCL 21功能的机制。低分子量肝素也强烈抑制CCL 21粘附和趋化性。因此，低分子量肝素可能是有效的治疗剂，通过靶向CCL 21调节T细胞浸润，减少T细胞浸润性自身免疫性疾病的病理。
The chemokine CCL21, also known as Exodus-2/6-Ckine/secondary lymphoid-tissue chemokine/T cell activator protein-4, is the most potent stimulator of T cell migration and adhesion yet described. Endothelial heparin-like glycosaminoglycans (GAGs) are thought to present chemokines at sites of inflammation, maintaining a local concentration gradient to which leukocytes can respond. In contrast, this study found that GAGs markedly inhibit the ability of CCL21 to stimulate T cell adhesion and chemotaxis. Enzymes, such as heparinase, that split GAGs into component-sulfated saccharides abrogate this inhibition, suggesting a mechanism for local tissue regulation of CCL21 function. Low-molecular-weight heparins also strongly inhibit CCL21 adhesion and chemotaxis. Therefore, low-molecular-weight heparins may be effective therapeutic agents in decreasing the pathology of T cell-infiltrative autoimmune diseases by targeting the CCL21 regulation of T cell infiltration.