Neutrophil transendothelial migration requires the activities of a number of cell-surface receptors, including ICAM-1 and JAM-C on the endothelial cell, LFA-1 and Mac-1 on the neutrophil. Neutrophil adhesion to endothelial cells triggers cytoskeletal reorganization in the endothelial cell prior to and accompanying transmigration. I propose to determine the following: 1) What cytoplasmic proteins bind to the C-terminal cytoplasmic tail of ICAM-1, possibly as targets for modification? 2) What are the effects of disrupting the interactions between ICAM-1 and its cytoplasmic targets on leukocyte transendothelial migration, the distribution of ICAM-1 on the endothelial cell surface, and cytoskeletal remodeling? 3) What effect does the blocking of JAM-C function have on leukocyte transendothelial migration? 4) Does JAM-C interact with the cytoskeleton directly? 5) Is JAM-C involved in intracellular signaling? The information gained from these studies will help delineate the ICAM-1 dependent mechanism underlying leukocyte transmigration and may define new therapeutic targets for immune and inflammatory diseases. ? ? ?
| Alcaide, Pilar; Auerbach, Scott; Luscinskas, Francis W (2009) Neutrophil recruitment under shear flow: it's all about endothelial cell rings and gaps. Microcirculation 16:43-57 |
