Genetic transfer of fusion proteins effectively inhibits VCAM-1-mediated cell adhesion and transmigration via inhibition of cytoskeletal anchorage
Christoph E Hagemeyer, Ingo Ahrens, Nicole Bassler, Natia Dschachutaschwili, Yung C Chen, Steffen U Eisenhardt, Christoph Bode, Karlheinz Peter
Journal of Cellular and Molecular Medicine | WILEY | Published : 2010
The adhesion of leukocytes to endothelium plays a central role in the development of atherosclerosis and thus represents an attractive therapeutic target for anti-atherosclerotic therapies. Vascular cell adhesion molecule-1 (VCAM-1) mediates both the initial tethering and the firm adhesion of leukocytes to endothelial cells. Our work evaluates the feasibility of using the cytoskeletal anchorage of VCAM-1 as a target for gene therapy. As a proof of concept, integrin alphaIIbbeta3-mediated cell adhesion with clearly defined cytoskeletal anchorage was tested. We constructed fusion proteins containing the intracellular domain of beta3 placed at various distances to the cell membrane. Using cell ..View full abstract
Awarded by Deutsche Forschungsgemeinschaft (DFG)
N.B., K.P. and C.E.H. are supported by the National Health and Medical Research Council of Australia. K.P. is supported by the Heart Foundation of Australia. C.E.H. and I.A. are supported by the Deutsche Forschungsgemeinschaft (DFG Ha 529/-1 & Ah 18/-1, respectively). We thank Drs. S. Marheineke and J. Lee for technical support and Drs. A. Straub and B. Smith for critical reading of the manuscript.