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Gene/Protein
Disease
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Target Concepts:
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Query: UMLS:C0014070 (
encephalomyelitis
)
13,017
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Extracellular vesicles (EVs) are emerging as potent mediators of intercellular communication with roles in inflammation and disease. In this study, we examined the role of EVs from blood plasma (pEVs) in an experimental autoimmune
encephalomyelitis
mouse model of central nervous system demyelination. We determined that pEVs induced a spontaneous relapsing-remitting disease phenotype in MOG
35-55
-immunized C57BL/6 mice. This modified disease phenotype was found to be driven by CD8+ T cells and required
fibrinogen
in pEVs. Analysis of pEVs from relapsing-remitting multiple sclerosis patients also identified
fibrinogen
as a significant portion of pEV cargo. Together, these data suggest that
fibrinogen
in pEVs contributes to the perpetuation of neuroinflammation and relapses in disease.
...
PMID:Extracellular vesicle fibrinogen induces encephalitogenic CD8+ T cells in a mouse model of multiple sclerosis. 3096 24
In a variety of diseases, from benign to life-threatening ones, inflammation plays a major role. Monitoring the intensity and extent of a multifaceted inflammatory process has become a cornerstone in diagnostics and therapy monitoring. However, the current tools lack the ability to provide insight into one of its most crucial aspects, namely, the alteration of the extracellular matrix (ECM). Using a radiolabeled platelet glycoprotein VI-based ECM-targeting fusion protein (GPVI-Fc), we investigated how binding of GPVI-Fc on fibrous tissue could uncover the progression of several inflammatory disease models at different stages (rheumatoid arthritis, cutaneous delayed-type hypersensitivity, lung inflammation and experimental autoimmune
encephalomyelitis
).
Methods:
The fusion protein GPVI-Fc was covalently linked to 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) and subsequently labeled with
64
Cu. We analyzed noninvasively
in vivo
64
Cu-GPVI-Fc accumulation in murine cutaneous delayed-type hypersensitivity, anti-glucose-6-phosphate isomerase serum-induced rheumatoid arthritis, lipopolysaccharide-induced lung inflammation and an experimental autoimmune
encephalomyelitis
model. Static and dynamic Positron Emission Tomography (PET) of the radiotracer distribution was performed
in vivo
, with
ex vivo
autoradiography confirmation, yielding quantitative accumulation and a distribution map of
64
Cu-GPVI-Fc.
Ex vivo
tissue histological staining was performed on harvested samples to highlight the fusion protein binding to collagen I, II and III, fibronectin and
fibrinogen
as well as the morphology of excised tissue.
Results:
64
Cu-GPVI-Fc showed a several-fold increased uptake in inflamed tissue compared to control tissue, particularly in the RA model, with a peak 24 h after radiotracer injection of up to half the injected dose. Blocking and isotype control experiments indicated a target-driven accumulation of the radiotracer in the case of chronic inflammation. Histological analysis confirmed a prolonged accumulation at the inflammation site, with a pronounced colocalization with the different components of the ECM (collagen III and fibronectin notably). Binding of the fusion protein appeared to be specific to the ECM but unspecific to particular components.
Conclusion:
Imaging of
64
Cu-GPVI-Fc accumulation in the ECM matrix appears to be a promising candidate for monitoring chronic inflammation. By binding to exposed fibrous tissue (collagen, fibronectin, etc.) after extravasation, a new insight is provided into the fibrotic events resulting from a prolonged inflammatory state.
...
PMID:Imaging fibrosis in inflammatory diseases: targeting the exposed extracellular matrix. 3124 29
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