Stromal cell-derived factor 1 (CXCL12) induces monocyte migration into human synovium transplanted onto SCID mice
Stromal cell-derived factor 1 (CXCL12) induces monocyte migration into human synovium transplanted onto SCID mice
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DOI：
10.1002/art.10102
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发表时间：
2002-03-01
影响因子：
--
通讯作者：
Pitzalis, C
中科院分区：
文献类型：
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作者：
Blades, MC;Ingegnoli, F;Pitzalis, C
客观的。单核细胞/巨噬细胞迁移至关节的机制涉及一系列整合的粘附和信号转导事件，其中趋化因子及其受体密切相关。本研究旨在调查基质细胞衍生因子 1 (SDF-1)（一种 CXC 趋化因子 (CXCL12)）在单核细胞/巨噬细胞滑膜定位中发挥关键作用的假设。方法。通过免疫组织化学和双重免疫荧光检查类风湿性关节炎 (RA) 和骨关节炎滑膜和移植物 SDF-1、肿瘤坏死因子 α (TNFα) 以及人类和小鼠血管标志物中 SDF-1 和 CXC 受体 4 (CXCR4) 的表达。通过检查早幼粒单核细胞 U937 细胞在移植到 SCID 小鼠滑膜组织中的定位，研究了 SDF-1 调节单核细胞迁移到关节的功能能力。将 SDF-1、TNFα 或盐水注射到移植部位，并通过紫外显微镜检测移植物中荧光标记的 U937 细胞（静脉注射）的数量来确定反应。结果。 SDF-1 和 CXCR4 在 RA 滑膜中的 CD68+ 细胞中高表达。 SDF-1 在体外和体内以剂量依赖性方式诱导 U937 细胞迁移，并且在体内，SDF-1 比 TNFα 更有效。与 TNFα 相比，SDF-1 不会在移植微血管系统中诱导细胞内粘附分子 I。此外，移植物内注射SDF-1并没有上调TNFα，反之亦然。结论。这项研究首次证明，SDF-1 在注射到滑膜移植物中时在体内具有功能。此外，SDF-1 比 TNFα 更有效，并且其作用机制似乎是自主的。因此，SDF-1可能是一种重要的TNF独立分子，参与炎症效应细胞迁移和保留在关节中。
Objective. The mechanisms by which monocyte/ macrophage cells migrate to the joint involve a series of integrated adhesion and signaling events in which chemokines and their receptors are strongly implicated. This study was undertaken to investigate the hypothesis that stromal cell-derived factor 1 (SDF-1), a CXC chemokine (CXCL12), plays a critical role in monocyte/ macrophage localization to synovium.Methods. SDF-1 and CXC receptor 4 (CXCR4) expression in rheumatoid arthritis (RA) and osteoarthritis synovium and graft SDF-1, tumor necrosis factor alpha (TNFalpha), and human and murine vascular markers were examined by immunohistochemistry and double-immunofluorescence. The functional capacity of SDF-1 to modulate monocyte migration into joints was investigated by examining the localization of promyelomonocytic U937 cells into synovial tissue transplanted into SCID mice. SDF-1, TNFalpha, or saline was injected into graft sites and response determined by the number of fluorescently labeled U937 cells (injected intravenously) detected in grafts by ultraviolet microscopy.Results. SDF-1 and CXCR4 were highly expressed in CD68+ cells in the RA synovium. SDF-1 induced U937 cell migration in vitro and in vivo in a dose-dependent manner and, in vivo, SDF-1 was more effective than TNFalpha. In contrast to TNFalpha, SDF-1 did not induce intracellular adhesion molecule I in transplant microvasculature. Furthermore, intragraft injection of SDF-1 did not up-regulate TNFalpha, or vice versa.Conclusion. This study demonstrates, for the first time, that SDF-1 is functional in vivo when injected into synovial grafts. In addition, SDF-1 is more potent than TNFalpha, and its mechanisms of action appear to be autonomous. Therefore, SDF-1 may be an important TNF-independent molecule involved in the migration to and retention of inflammatory effector cells in the joint.