Gadopentetate meglumine activates mast cells to cause IgE-independent allergic reactions both in vitro and in vivo

Gadopentetate meglumine (Gd-DTPA) is a commonly used magnetic resonance imaging (MRI) enhancer in the clinic for improving the clarity of MRI. Reports have shown that severe anaphylactoid reactions can occur after intravenous injections, whereas the underlying mechanisms remain undefined. In this study, the effects of Gd-DTPA in causing allergic like reactions and mast cells (MCs) activation were investigated both in vitro and in vivo. Gd-DTPA induced a severe hand paw swelling and body temperature decrease in murine topical cutaneous allergy model, and murine systemic allergy model. Meanwhile, serum IgE was not significantly changed. Histamine, tryptase, and cytokines release in mice serum and LAD2 cells supernatant were increased significantly both in mice serum and LAD2 supernatant after treated with Gd-DTPA. Subsequently, the changes in mRNA levels after Gd-DTPA activated MCs were analyzed by RNAseq and found to be related to inflammation signaling pathways. The study provides a demonstration for the adverse reaction mechanism of Gd-DTPA and its safe use in clinic.