Gadolinium-promoted precipitation of calcium phosphate is associated with profibrotic activation of RAW 264.7 macrophages.
Gadolinium-based contrast agents are now being linked to nephrogenic systemic fibrosis (NSF). The exact mechanism by which gadolinium species act in the pathogenesis of NSF is not fully understood. In this study, we evaluated the effect of gadolinium chloride (GdCl(3)) on the precipitation of calcium phosphate, and examined the role of the gadolinium-containing precipitates in the profibrotic activation of macrophages. In a free-drift system, the induction time was markedly reduced with increasing concentration of GdCl(3), accompanied by alterations of morphology and composition of the precipitates. In complete cell culture medium, the addition of GdCl(3) resulted in formation of particles around 200-300 nm. In an in vitro cellular model with RAW 264.7 macrophages, GdCl(3) increased the production of TGF-beta1 and IL-6 via the activation of PKC and ERK signaling pathway. Our findings demonstrate that GdCl(3) promotes calcium phosphate precipitation and induces profibrotic activation of macrophages.
Gou
Bao-Di
BD
Department of Chemical Biology, Peking University School of Pharmaceutical Sciences, Beijing, PR China. b.gou@bjmu.edu.cn
Bian
Sha
S
Zhang
Tian-Lan
TL
Wang
Kui
K
D000818:Animals; D002130:Calcium Phosphates / Q000737:chemistry* / Q000633:toxicity; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D011232:Chemical Precipitation; D005355:Fibrosis / Q000139:chemically induced* / Q000473:pathology; D005682:Gadolinium / Q000737:chemistry* / Q000633:toxicity; D015850:Interleukin-6 / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D010316:Particle Size; D013052:Spectrometry, X-Ray Emission; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D002130:Calcium Phosphates; D015850:Interleukin-6; D053773:Transforming Growth Factor beta1; C020243:calcium phosphate; D005682:Gadolinium; C038958:gadolinium chloride