Cell surface-anchored SR-PSOX/CXC chemokine ligand 16 mediates firm adhesion of CXC chemokine receptor 6-expressing cells
Cell surface-anchored SR-PSOX/CXC chemokine ligand 16 mediates firm adhesion of CXC chemokine receptor 6-expressing cells
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DOI：
10.1189/jlb.1003465
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发表时间：
2004-02-01
影响因子：
5.5
通讯作者：
Yonehara, S
中科院分区：
文献类型：
--
作者：
Shimaoka, T;Nakayama, T;Yonehara, S
树突状细胞（DCs）与T细胞或自然杀伤T细胞（NKT）的直接接触在初次和二次免疫应答中起重要作用。SR-PSOX/CXC趋化因子配体16（CXCL 16）选择性表达于DC和巨噬细胞上，是氧化低密度脂蛋白的清道夫受体，也是G蛋白偶联受体CXC趋化因子受体6（CXCR 6）的趋化因子配体，表达于活化的T细胞和NKT细胞上。SR-PSOX/CXCL 16是第二种跨膜型趋化因子，其趋化因子结构域融合到粘蛋白样茎上，结构与fractalkine（FNK）非常相似。在这里，我们证明了SR-PSOX/CXCL 16作为表达CXCR 6的细胞的细胞粘附分子的功能，其方式与FNK作为表达CX 3C趋化因子受体1（CX（3）CR 1）的细胞的细胞粘附分子的功能相同，而不需要CX（3）CR 1介导的信号转导或整合素活化。SR-PSOX/CXCL 16的趋化因子结构域介导CXCR 6表达细胞的粘附，其不受百日咳毒素（Galphai蛋白阻断剂）处理的损害，百日咳毒素抑制SR-PSOX/CXCL 16诱导的CXCR 6表达细胞的趋化性。此外，通过用金属蛋白酶抑制剂处理SR-PSOX/CXCL 16表达细胞，其增加SRPSOX/CXCL 16的表面表达水平，粘附活性被上调。因此，SR-PSOX/CXCL 16是一种独特的分子，不仅将T细胞和NKT细胞吸引到DC，而且还支持它们与DC的牢固粘附。
Direct contacts between dendritic cells (DCs) and T cells or natural killer T (NKT) cells play important roles in primary and secondary immune responses. SR-PSOX/CXC chemokine ligand 16 (CXCL16), which is selectively expressed on DCs and macrophages, is a scavenger receptor for oxidized low-density lipoprotein and also the chemokine ligand for a G protein-coupled receptor CXC chemokine receptor 6 (CXCR6), expressed on activated T cells and NKT cells. SR-PSOX/CXCL16 is the second transmembrane-type chemokine with a chemokine domain fused to a mucin-like stalk, a structure very similar to that of fractalkine (FNK). Here, we demonstrate that SR-PSOX/CXCL16 functions as a cell adhesion molecule for cells expressing CXCR6 in the same manner that FNK functions as a cell adhesion molecule for cells expressing CX3C chemokine receptor 1 (CX(3)CR1) without requiring CX(3)CR1-mediated signal transduction or integrin activation. The chemokine domain of SR-PSOX/CXCL16 mediated the adhesion of CXCR6-expressing cells, which was not impaired by treatment with pertussis toxin, a Galphai protein blocker, which inhibited chemotaxis of CXCR6-expressing cells induced by SR-PSOX/CXCL16. Furthermore, the adhesion activity was up-regulated by treatment of SR-PSOX/CXCL16-expressing cells with a metalloprotease inhibitor, which increased surface expression levels of SRPSOX/CXCL16. Thus, SR-PSOX/CXCL16 is a unique molecule that not only attracts T cells and NKT cells toward DCs but also supports their firm adhesion to DCs.