First Author | Muczynski V | Year | 2016 |
Journal | Blood | Volume | 127 |
Issue | 6 | Pages | 778-86 |
PubMed ID | 26608330 | Mgi Jnum | J:231550 |
Mgi Id | MGI:5771740 | Doi | 10.1182/blood-2015-05-647032 |
Citation | Muczynski V, et al. (2016) Macrophage receptor SR-AI is crucial to maintain normal plasma levels of coagulation factor X. Blood 127(6):778-86 |
abstractText | 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 mug/mL) to the extracellular domain of SR-AI. Altogether, we demonstrate that macrophages regulate FX plasma levels in an SR-AI-dependent manner. |