Hansch Andreas, Frey Oliver, Sauner Dieter, Hilger Ingrid, Haas Michael, Malich Ansgar, Bräuer Rolf, Kaiser Werner A
Institute of Diagnostic and Interventional Radiology, Fredrich Schiller University Jena, Jena, Germany.
Arthritis Rheum. 2004 Mar;50(3):961-7. doi: 10.1002/art.20112.
To visualize early experimental arthritis with near-infrared fluorescence (NIRF) imaging in a murine model of antigen-induced arthritis (AIA).
The target of NIRF was the F4/80 antigen present on the surface of macrophages infiltrating the inflamed synovial membrane. Imaging was performed using anti-F4/80 monoclonal antibodies (mAb) labeled with Cy5.5 fluorochrome. On day 7 of AIA, 6 mice received an intravenous (IV) injection of labeled mAb; control AIA mice (n = 6) received an IV injection of Cy5.5-labeled isotype control antibody. NIRF imaging was performed before injection (baseline) and until 72 hours thereafter. Histologic evaluation of arthritis severity and immunohistochemical assessment of F4/80 antigen density were also performed on day 7.
NIRF imaging showed an accumulation of fluorochrome probes in the inflamed knee joints and, to a lesser extent, in the contralateral (nonarthritic) knee joints. The signal induced by mAb F4/80 was clearly higher than that generated by the isotype control. Accumulation of fluorochrome probes in the joints was confirmed histologically by confocal laser scanning microscopy.
The use of fluorochromes allows imaging of arthritis in the near-infrared range. Accumulation in the contralateral, nonarthritic knee joints can be explained by the presence of sentinel macrophages in normal synovium or by a mild contralateral response due to systemic activation or neurogenic mechanisms.
在抗原诱导性关节炎(AIA)小鼠模型中,利用近红外荧光(NIRF)成像技术观察早期实验性关节炎。
NIRF的靶点是浸润于炎症滑膜表面巨噬细胞上存在的F4/80抗原。使用标记有Cy5.5荧光染料的抗F4/80单克隆抗体(mAb)进行成像。在AIA第7天,6只小鼠接受标记mAb的静脉注射;对照AIA小鼠(n = 6)接受Cy5.5标记的同型对照抗体静脉注射。在注射前(基线)及之后直至72小时进行NIRF成像。在第7天还进行了关节炎严重程度的组织学评估和F4/80抗原密度的免疫组织化学评估。
NIRF成像显示荧光染料探针在炎症膝关节中积聚,在对侧(非关节炎)膝关节中也有较少程度的积聚。mAb F4/80诱导的信号明显高于同型对照产生的信号。通过共聚焦激光扫描显微镜在组织学上证实了荧光染料探针在关节中的积聚。
荧光染料的使用使得能够在近红外范围内对关节炎进行成像。对侧非关节炎膝关节中的积聚可通过正常滑膜中前哨巨噬细胞的存在或由于全身激活或神经源性机制引起的轻度对侧反应来解释。