Abstract：
Gadolinium is a component of the MRI contrast agent Dotarem. Although Dotarem is the least toxic among MRI contrasts used, gadolinium present in Dotarem accumulates for many years in various organs and tissues exerting toxic effects. We showed previously that gadolinium remains in macrophages for at least 7 days after exposure to Dotarem. However, very little is known about the effect of gadolinium retention on the immune cells such as macrophages. We studied the effect of 1-day and 7-day retention of gadolinium on various functions and molecular pathways of macrophages. Gadolinium retention for 7 days decreased macrophage adhesion and motility and dysregulated the expression of adhesion and fibrotic pathway-related proteins such as Notch1 and its ligand Jagged1, adhesion/migration-related proteins PAK1 and Shp1, immune response-related transcription factors Smad3 and TCF19, and chemokines CXCL10 and CXCL13, and dysregulated the mRNA expression of fibrosis-related genes involved in extracellular matrix (ECM) synthesis, such as Col6a1, Fibronectin, MMP9, and MMP12. It also completely (below a level of detection) shut down the transcription of anti-inflammatory M2 macrophage polarization marker the Arg-1. Such changes, if they occur in MRI patients, can be potentially detrimental to the patient\'s immune system and immune response-related processes.
摘要：
钆是MRI造影剂Dotarem的成分。尽管Dotarem是使用的MRI对比度中毒性最小的，Dotarem中存在的钆在各种器官和组织中积累多年，发挥毒性作用。我们先前表明，暴露于Dotarem后，g在巨噬细胞中保留至少7天。然而,对钆滞留对巨噬细胞等免疫细胞的影响知之甚少。我们研究了钆保留1天和7天对巨噬细胞各种功能和分子途径的影响。钆保留7天降低了巨噬细胞的粘附和运动，并失调了粘附和纤维化途径相关蛋白的表达，例如Notch1及其配体Jagged1，粘附/迁移相关蛋白PAK1和Shp1，免疫应答相关转录因子Smad3和TCF19以及趋化因子CXCL10和CXCL13，并失调了参与细胞外基质（ECM）合成的纤维化相关基因的mRNA表达，如Col6a1，纤连蛋白，MMP9和MMP12。它还完全（低于检测水平）关闭抗炎M2巨噬细胞极化标记Arg-1的转录。这样的变化,如果它们发生在MRI患者中，可能对患者的免疫系统和与免疫反应相关的过程有潜在的损害。
