| First Author | Do C | Year | 2019 |
| Journal | J Invest Dermatol | Volume | 139 |
| Issue | 10 | Pages | 2134-2143.e2 |
| PubMed ID | 30978353 | Mgi Jnum | J:285810 |
| Mgi Id | MGI:6387668 | Doi | 10.1016/j.jid.2019.03.1145 |
| Citation | Do C, et al. (2019) Nephrogenic Systemic Fibrosis Is Mediated by Myeloid C-C Chemokine Receptor 2. J Invest Dermatol 139(10):2134-2143.e2 |
| abstractText | Gadolinium-based contrast agents are implicated in several pathologic abnormalities (long-term retention in vital organs such as the skin and the brain) and are the cause of a sometimes fatal condition in patients, nephrogenic systemic fibrosis. Bone marrow-derived fibrocytes and the monocyte chemoattractant protein-1 inflammatory pathway have been implicated as mediators of the adverse effects induced by gadolinium-based contrast agents. Mechanistic studies are scant; therefore, a mouse model of nephrogenic systemic fibrosis was established. Dermal cellularity was increased in contrast-treated green fluorescent protein (GFP) chimeric mice. GFP in the skin and fibrosis were increased in the contrast-treated chimeric animals. Monocyte chemoattractant protein-1 and C-C chemokine receptor 2 were increased in the tissues from contrast-treated mice. C-C chemokine receptor 2-deficient recipients of GFP-expressing marrow had an abrogation of gadolinium-induced pathology and displayed less GFP-positive cells in the skin. Wild-type animals that received C-C chemokine receptor 2-deficient bone marrow had a complete abrogation of dermal pathology. That GFP levels and expression increase in the skin, in tandem with a fibrocyte marker, supports the blood-borne circulating fibrocyte hypothesis of the disease. As of now, fibrocyte trafficking has yet to be demonstrated. Importantly, our data demonstrate that the monocyte chemoattractant protein-1/C-C chemokine receptor 2 axis plays a critical role in the pathogenesis of nephrogenic systemic fibrosis. |
