Macrophage receptor SR-AI is crucial to maintain normal plasma levels of coagulation factor X

Beside its classical role in the coagulation cascade, coagulation Factor X (FX) is involved in several major biological processes including inflammation and enhancement of virus-induced immune responses. We recently reported that the long circulatory half-life of FX is linked to its interaction with liver resident macrophages. Importantly, we now observed that macrophages but not undifferentiated monocytes support this interaction. Using cell-biology approaches with primary and THP1-derived macrophages as well as transfected cells, we further identified the scavenger receptor type A member I (SR-AI) to be a macrophage-specific receptor for FX. This result was confirmed using SR-AI deficient mice, which exhibit reduced circulating levels of FX in vivo and loss of FX-macrophage interactions in vitro. Binding studies using purified proteins revealed that FX binds specifically (half-maximal binding 3 microgram/ml) to the extracellular domain of SR-AI. Altogether, we demonstrate that macrophages regulate FX plasma levels in an SR-AI dependent manner.