Cutting edge: Activity of human adult microglia in response to CC chemokine ligand 21
Cutting edge: Activity of human adult microglia in response to CC chemokine ligand 21
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DOI：
10.4049/jimmunol.172.5.2744
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发表时间：
2004-03-01
影响因子：
4.4
通讯作者：
Biber, K
中科院分区：
文献类型：
--
作者：
Dijkstra, IM;Hulshof, S;Biber, K
大约50种已知的趋化因子分为不同的亚家族：CXC、CC、CX 3C和C。尽管趋化因子的信号传导通常是混杂的，但几乎没有观察到这些不同趋化因子类别的成员之间的信号传导事件。迄今为止唯一已知的例外是鼠CC趋化因子配体（CCL）21（次级淋巴组织趋化因子，Exodus-2，6Ckine），其结合并激活鼠CXC趋化因子受体CXCR 3。然而，这种例外在人类中尚未发现。在这项研究中，我们提供的证据表明，人类CCL 21是一个功能性配体内源性表达的CXCR 3在人类成人小胶质细胞。在不存在CCR 7表达的情况下，CCL 21以与CXCR 3配体CXC趋化因子配体9（由IFN-γ诱导的单核因子）和CXC趋化因子配体10（IFN-γ诱导蛋白-10）相似的效率诱导人小胶质细胞的趋化性。因为人CCL 21在CXCR 3转染的HEK 293细胞中未显示任何作用，这表明CXCR 3信号传导取决于表达CXCR 3的细胞背景。
The approximately 50 known chemokines are classified in distinct subfamilies: CXC, CC, CX3C, and C. Although the signaling of chemokines often is promiscuous, signaling events between members of these distinct chemokine classes are hardly observed. The only known exception so far is the murine CC chemokine ligand (CCL)21 (secondary lymphoid tissue chemokine, Exodus-2, 6Ckine), which binds and activates the murine CXC chemokine receptor CXCR3. However, this exception has not been found in humans. In this study, we provide evidence that human CCL21 is a functional ligand for endogenously expressed CXCR3 in human adult microglia. In absence of CCR7 expression, CCL21 induced chemotaxis of human microglia with efficiency similar to the CXCR3 ligands CXC chemokine ligand 9 (monokine induced by IFN-gamma) and CXC chemokine ligand 10 (IFN-gamma-inducible protein-10). Because human CCL21 did not show any effects in CXCR3-transfected HEK293 cells, it is indicated that CXCR3 signaling depends on the cellular background in which the CXCR3 is expressed.