Schematic model of FX regulation by SR-AI and PTX2. (A) Under physiological conditions, part of FX circulates in association with PTX2 as a macromolecular complex. Upon binding to SR-AI at the surface of macrophages, the presence of PTX2 prevents receptor-mediated endocytosis, which results in the protective mechanism that maintains elevated plasma levels of FX. FX that arrives alone at the macrophage surface forms a complex with macrophage-produced PTX2. (B) In the absence of SR-AI, the protective interaction with the macrophages is abolished, which ultimately leads to increased clearance of FX, associated with reduced circulating levels of both FX and PTX2. (C) In the absence of PTX2, FX is no longer protected against SR-AI–mediated endocytosis. Again, the absence of the protective interaction is associated with increased FX clearance (its regular clearance pathway and also in an SR-AI–mediated fashion by macrophages), resulting in reduced plasma concentrations. (D) In the absence of FX, PTX2 is no longer protected against SR-AI–mediated endocytosis. Again, the absence of the protective interaction is probably with increased PTX2 clearance (via its regular clearance pathway and also in an SR-AI–mediated fashion by macrophages), resulting in reduced plasma concentrations.