This dataset presents results of an in vivo model of gadolinium-based contrast agent-induced systemic fibrosis. Figure 1 demonstrates that gadolinium-based contrast agent treatment induces dermal fibrosis and hypercellularity of the same magnitude in patients afflicted with ‘nephrogenic’ systemic fibrosis. Electron microscopy demonstrated that systemic gadolinium treatment induced the formation of multinucleated giant cells in the dermis laden with electron-dense, mesh-like nanostructures. Scanning transmission electron microscopy with energy-dispersive spectroscopy revealed that the electron-dense nanoparticles were gadolinium rich. Figure 2 represents the first chimeric model of mice and gadolinium-induced systemic fibrosis (to our knowledge). Lethally-irradiated mice with 5/6 nephrectomy (to model renal insufficiency) were salvaged with bone marrow from green fluorescent protein-expressing donors. After engraftment, the group was randomized to gadolinium-based contrast agent treatment or control. Gadolinium-based contrast agent treatment led to dermal fibrosis, dermal hypercellularity, and an increase in myeloid cells in the dermis. Figure 3 represents the expression of fibrocyte markers (CD34, CD45RO), the myofibroblast marker α smooth muscle actin, and a marker of alternatively-activated macrophages—CD163—in the dermis. Figure 4 demonstrates an increase of the monocyte chemoattractant protein and its receptor, the C-C chemokine receptor 2, in the dermis of the gadolinium-based contrast-treated group. Figure 5 shows the impact of recipient deficiency of the C-C chemokine receptor 2 in a chimeric model of gadolinium-based contrast agent-induced fibrosis and dermal cellularity. Figure 6 depicts the inverse of the experiment shown in Figure 5; wild-type recipient mice were lethally irradiated and salvaged with C-C chemokine receptor 2-deficient bone marrow (with a red fluorescent tag). Skin fibrosis and dermal cellularity were abrogated in the group treated with gadolinium-based contrast agent.
Do, Catherine; Viktor Drel; Chunyan Tan; Duck-Yoon Lee; and Brent Wagner. "'Nephrogenic' systemic fibrosis is mediated by myeloid C-C chemokine receptor 2 dataset." (2019). https://digitalrepository.unm.edu/kinm/1