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Gadolinium-containing magnetic resonance image contrast agent promotes fibrocyte differentiation

โœ Scribed by Varsha Vakil; Joanna J. Sung; Marta Piecychna; Jeffrey R. Crawford; Phillip Kuo; Ali K. Abu-Alfa; Shawn E. Cowper; Richard Bucala; Richard H. Gomer


Book ID
102375462
Publisher
John Wiley and Sons
Year
2009
Tongue
English
Weight
413 KB
Volume
30
Category
Article
ISSN
1053-1807

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โœฆ Synopsis


Abstract

Gadoliniumโ€containing magnetic resonance imaging (MRI) contrast agents such as Omniscan are associated with nephrogenic systemic fibrosis (NSF). To determine if Omniscan can affect the differentiation of monocytes into fibroblastโ€like cells called fibrocytes that are found in the fibrotic lesions of NSF, peripheral blood mononuclear cells (PBMCs) from NSF patients, hemodialysis patients without NSF, and healthy, renally sufficient controls were exposed to Omniscan in a standardized in vitro fibrocyte differentiation protocol. When added to PBMCs, the gadoliniumโ€containing MRI contrast agent Omniscan generally had little effect on fibrocyte differentiation. However, 10^โˆ’8^ to 10^โˆ’3^ mg/mL Omniscan reduced the ability of the fibrocyte differentiation inhibitor serum amyloid P (SAP) to decrease fibrocyte differentiation in PBMCs from 15 of 17 healthy controls and one of three NSF patients. Omniscan reduced the ability of SAP to decrease fibrocyte differentiation from purified monocytes, indicating that the Omniscan effect does not require the presence of other cells (such as T cells) in the PBMCs. Omniscan also reduced the ability of a different fibrocyte differentiation inhibitor, interleukinโ€12, to decrease fibrocyte differentiation. These data suggest that Omniscan interferes with the regulatory action of signals that inhibit the differentiation of monocytes to fibrocytes. J. Magn. Reson. Imaging 2009;30:1284โ€“1288. ยฉ 2009 Wileyโ€Liss, Inc.


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Scheme 1. Reduction-controlled condensation of 1 to assemble gadolinium-containing nanoparticles (Gd NPs). Compound 2 is the control probe that cannot be reduced to induce condensation. [