The proposal involves P-selectin, a transmembrane receptor on the surface of activated platelets and endothelial cells, that binds to neutrophils, monocytes and other selected cell populations. The proposal utilizes mice that are severely deficient or altered in P-selectin, and it involves three aims. First, the phenotype of P-selectin deficient mice will be analysed in terms of platelet function in models of wound repair, inflammation, atherosclerosis and metastases. Second, the individual contribution of P- selectin in the same models will be determined using chimeric mice produced through bone marrow transplantation and lacking either platelet or endothelial P-selectin. Third, the expression of P-selectin on platelets and endothelium will be altered so that the protein is expressed on the surface in a constitutive manner instead of only on an activated cell surface. This would be accomplished by deleting the cytoplasmic domain of the adhesion receptor. The overall aim of the proposal is to understand the role of P-selectin at the level of individual physiologic functions and at the level of distribution of the protein within platelets or endothelial cells.
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| Burger, Peter C; Wagner, Denisa D (2003) Platelet P-selectin facilitates atherosclerotic lesion development. Blood 101:2661-6 |
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