Characterization of the Fgl2-prothrombinase binding protein

grantor: University of TorontoThe inflammatory cascade and the coagulation system are intimately connected; several coagulation proteins have been demonstrated to regulate inflammatory events. Studies have shown that fibrinogen is able to promote cellular adhesion and transendothelial migration through interactions with ICAM-1 and Mac-1, prompting speculation that related proteins may have similar roles. Fgl2 prothrombinase shares significant homology to the fibrinogen-ã chain; in particular the P1 domain of fibrinogen, which is responsible for interactions with Mac-1, is highly conserved in Fgl2. We hypothesized that soluble Fgl2 has an immunomodulatory effect through interactions with a cell-surface receptor. We further speculated that Fgl2 interacts with this putative receptor through its fibrinogen-related domain, and may bind to Mac-1 through the conserved P1 region. We found that Fgl2 binds to RAW 264.7 cells in a specific and dose-dependent manner (K d = 185 nM), and that this binding is not dependent on Mac-1.M.Sc