'Nephrogenic' systemic fibrosis is mediated by myeloid C-C chemokine receptor 2.

08:00 EDT 9th April 2019 | BioPortfolio

Summary of "'Nephrogenic' systemic fibrosis is mediated by myeloid C-C chemokine receptor 2."

Gadolinium-based contrast agents are implicated in several pathologic abnormalities (long-term retention in vital organs such as the skin and brain) and are the cause of a sometimes fatal condition in patients, 'nephrogenic' systemic fibrosis (NSF). Bone marrow-derived fibrocytes and the monocyte chemoattractant protein 1 (MCP1) inflammatory pathway have been implicated as mediators of adverse effects induced by gadolinium-based contrast agents. Mechanistic studies are scant. A mouse model of NSF was established. Dermal cellularity was increased in contrast-treated green fluorescent protein (GFP) chimeric mice. Skin GFP and fibrosis were all increased in the contrast-treated chimeric animals. MCP-1 and CCR-2 were increased in the tissues from contrast-treated mice. CCR2-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 CCR2-deficient marrow had a complete abrogation of dermal pathology. That GFP levels and expression increase in an involved organ, the skin, in tandem with a fibrocyte marker supports the blood-borne circulating fibrocyte hypothesis of the disease. Heretofore fibrocyte trafficking has yet to 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 NSF.


Journal Details

This article was published in the following journal.

Name: The Journal of investigative dermatology
ISSN: 1523-1747


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