Intracellular events in cerebral endothelial cells during the transmigration of monocytes

Lines connect the coordinator with its partners.

Project objective

Research objectives and content The entry of monocytes into the brain may be one of the key events in immune-mediated diseases of the brain, like multiple sclerosis. Interaction of monocytes with the cerebrovascular endothelium may be one of the initial processes in the development of the disease. In this project, the relationship between monocyte-induced signalling pathways within the brain endothelial cells, and the subsequent transmigration of monocytes across the blood-brain barrier will be explored. The study will elucidate the mechanism of monocyte migration at the molecular levelby defining the endothelial surface molecules engaged during the process and which are responsible for initiating signalling pathways leading to alterations in the arrangements of the cytoskeleton and tight junctions. The immortalized cell-lines RBE-4 and GP 8/3 are available within the Institute and form a valuable tool in the transmigration studies. The adhesion molecules involved in the transmigration process will be identified. This project will then focus on the intracellular signalling pathways coupled to these adhesion molecules. In particular the role of small GTP-biding proteins (e.g. rho) in the endothelial cytoskeletal rearrangement and tight junction organisation that occurs during the monocyte transvascular migration will be evaluated. Training content (objective, benefit and expected impact) This study will be the first to describe the role and possible correlation of signal transduction pathways and the transmigration of monocytes into the brain. The understanding of these processes may eventually lead to the identification of potential therapies for immune-mediated diseases of the central nervous system. Links with industry / industrial relevance (22) This project has no direct links with industry or other Community programmes

Original text from CORDIS.

Participants

• UNIVERSITY COLLEGE LONDON · LONDONCoordinatorUnited Kingdom

Links

• View on CORDIS