Abstract 5686: Stromal Cell-Derived Factor 1 (SDF-1) Signaling Regulates Platelet Migration

Platelets have been regarded as static cells that do not move once they adhere to a matrix. In contrast to the current opinion, we found that platelets were mobile, able to migrate over a surface, and transmigrated through a transwell membrane and endothelium toward a source of SDF-1(See Sketch 1 and Image 2 below). Platelet migration was regulated by SDF-1 signaling, which involves Phosphoinositol 3-Kinase (PI3-Kinase) and downstream SGK1 (Serum- and Glucocorticoid regulated Kinase-1). SGK1 is a central element in ion channel homeostasis that is crucial for cytoskeletal rearrangement. Thus, the regulation of platelet migration describes an entirely novel functional area of SGK1. In vivo transmigration experiments in mice using intravital microscopy showed platelet invasion into post-ischemic vascular areas, but significantly decreased invasion by murine SGK1 −/− platelets (see photomicrographs, Image 3 and Table 4). Corresponding in vitro transmigration experiments revealed that SGK1 −/− platelets show significantly decreased response to SDF-1 and migratory activity (Table 4). The potential of platelets to migrate may substantially redefine the role of platelets in the pathophysiology of vascular inflammation, subsequent atherosclerotic degeneration and vascular regeneration.