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.
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Funding
Support by the J.C. Walter Jr. Transplant Center fund at the Houston Methodist Hospital Foundation, and William Stamps Farish Fund. JW was supported by Texas Center for Superconductivity. JZK was supported by the subvention of the Polish Ministry of Education and Science, project no 612/2023 to JZK at WIM-PIB. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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Halasa, M., Uosef, A., Ubelaker, H.V. et al. Gadolinium retention effect on macrophages — a potential cause of MRI contrast agent Dotarem toxicity. Cell Tissue Res (2024). https://doi.org/10.1007/s00441-024-03885-8
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DOI: https://doi.org/10.1007/s00441-024-03885-8