Chronic inflammatory pathology of cartilage and bone represents a major source of damage tothe synovial joints observed in rheumatoid arthritis (RA). Although the precise etiology of thesediseases is often unknown, excessive leukocyte extravasation is a substantial contributor to thetissue damage/inflammation and our recent data show a prominent role of the plasma protein,Reelin in this process. Furthermore, we have now shown that it is possible, using anti-Reelinmonoclonal antibodies, to deplete the plasma of Reelin, which results in a significant reductionof a wide range of vascular adhesion molecule expression. Thus, in contrast to the currentmethods of depleting individual adhesion molecules or immune receptors, our anti-Reelinapproach systematically downregulates all major inflammation-driven adhesion proteins on thevascular endothelium. The purpose of this proposal is to demonstrate the role of Reelin in RAby 1) identifying high affinity Reelin antibodies and 2) validating the therapeutic potential ofmitigating chronic inflammatory milieu with an anti-Reelin antibody in an RA mouse model.
Public Health Relevance Statement: Project Narrative
Chronic inflammation contributes in a substantial way to the pathology observed in multiple chronic degenera-
tive diseases, including rheumatoid arthritis (RA). In this application, we explore the feasibility of targeting a
novel pro-inflammatory system, based on the interaction of Reelin with Apolipoprotein-ER2, to decrease
disease progression in a mouse model of human RA.
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