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

Vincent Muczynski, Amine Bazaa, Cécile Loubière, Amélie Harel, Ghislaine Cherel, Cécile V. Denis, Peter J. Lenting and Olivier D. Christophe

Key Points

  • SR-AI is the major receptor of FX at the macrophage surface.

  • Macrophages use SR-AI to control FX circulatory levels.


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 μg/mL) to the extracellular domain of SR-AI. Altogether, we demonstrate that macrophages regulate FX plasma levels in an SR-AI–dependent manner.

  • Submitted May 19, 2015.
  • Accepted November 17, 2015.
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