前沿：成年人类小胶质细胞对CC趋化因子配体21的反应活性

Cutting edge: activity of human adult microglia in response to CC chemokine ligand 21.

作者信息

Dijkstra Ineke M, Hulshof Sandra, van der Valk Paul, Boddeke Hendrikus W G M, Biber Knut

机构信息

Department of Medical Physiology, University of Groningen, Groningen, The Netherlands.

出版信息

J Immunol. 2004 Mar 1;172(5):2744-7. doi: 10.4049/jimmunol.172.5.2744.

DOI:10.4049/jimmunol.172.5.2744

PMID:14978072

Abstract

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.

摘要

已知的大约50种趋化因子被分为不同的亚家族：CXC、CC、CX3C和C。尽管趋化因子的信号传导通常是混杂的，但在这些不同趋化因子类别成员之间几乎观察不到信号传导事件。到目前为止，唯一已知的例外是小鼠CC趋化因子配体（CCL）21（二级淋巴组织趋化因子、Exodus-2、6Ckine），它能结合并激活小鼠CXC趋化因子受体CXCR3。然而，在人类中尚未发现这种例外情况。在本研究中，我们提供证据表明，人CCL21是成人人类小胶质细胞中内源性表达的CXCR3的功能性配体。在缺乏CCR7表达的情况下，CCL21诱导人类小胶质细胞趋化，其效率与CXCR3配体CXC趋化因子配体9（γ干扰素诱导的单核因子）和CXC趋化因子配体10（γ干扰素诱导蛋白10）相似。由于人CCL21在转染CXCR3的HEK293细胞中未显示任何作用，这表明CXCR3信号传导取决于CXCR3所表达的细胞背景。