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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.
This article was published in the following journal.
Name: The Journal of investigative dermatology
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The investigators will study the effect of imatinib mesylate (Glivec) in treatment of moderate to severe nephrogenic systemic fibrosis (NSF). So far there is no evidence of adequately eff...
The objective of this study is to prospectively monitor the incidence of adverse drug reactions, specifically NSF during routine use of gadoversetamide in a large number of patients with m...
Study Design: In this phase 4 study, all patients will receive 1 dose of Ablavar as part of an MRI examination in their routine clinical management. A standardized NSF questionnair...
The primary objective of this study is to determine any causative or associated factors contributing to the development of Nephrogenic Systemic Fibrosis (NSF), Nephrogenic Fibrosing Dermop...
This study aims to elucidate the role of Chemokine and chemokine receptor in the pathogenesis of Psoriasis by using human psoriasis skin xenograft SCID mouse model. The hypothesis is that ...
A chronic, acquired, idiopathic, progressive eruption of the skin that occurs in the context of RENAL FAILURE. It is sometimes accompanied by systemic fibrosis. The pathogenesis seems to be multifactorial, with postulated involvement of circulating fibrocytes. There is a strong association between this disorder and the use of gadolinium-based contrast agents.
Receptor for CHEMOKINE CX3CL1 expressed by lymphocytes, neurons, and GLIAL CELLS. Its interaction with CX3CL1 mediates CELL ADHESION and CELL MIGRATION. It also functions as a co-receptor with the CD4 ANTIGEN for HIV-1 in vitro.
An INTEFERON-inducible CXC chemokine that is specific for the CXCR3 RECEPTOR.
A CXCR6 receptor-binding chemokine that functions as a scavenger receptor for oxidized low density lipoprotein (OxLDL) when expressed by MACROPHAGES. Its secreted, or cytokine form induces a strong chemotactic response for MONOCYTES when it is expressed by DENDRITIC CELLS.
A C-C chemokine expressed by all tissues that functions as a chemoattractant for EOSINOPHILS and BASOPHILS. It binds to the CCR3 RECEPTOR.
Cytokines include chemokines, lymphokines, and monokines. Cells of the immune system communicate with one another by releasing and responding to chemical messengers called cytokines. These proteins are secreted by immune cells and act on other cells to...
Acne Dermatology Eczema Psoriasis Wound Care Dermatology is the medical specialty concerned with the diagnosis and treatment of skin disorders (Oxford Medical Dictionary). As well as studying how the skin works, dermatology covers...
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