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

Abstract

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 virusinduced 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 mg/mL) to the extracellular domain of SR-AI. Altogether, we demonstrate that macrophages regulate FX plasma levels in an SR-AI-dependent manner. (Blood. 2016;127(6):778-786)

Macrophage scavenger receptor SR-AI contributes to the clearance of von Willebrand factor

“…Briefly, human macrophages were differentiated from the THP1 acute monocytic leukemia cell line using phorbol 12-myristate 13-acetate, human macrophage colony-stimulating factor and human granulocyte-macrophage colony-stimulating factor as described elsewhere. 18 , 19 Non-transfected and stable HEK293 cell lines expressing human SR-AI were cultured as described presviously. 19 Murine macrophages were obtained from CD115 + cells as described by Breslin et al .…”

“… 18 , 19 Non-transfected and stable HEK293 cell lines expressing human SR-AI were cultured as described presviously. 19 Murine macrophages were obtained from CD115 + cells as described by Breslin et al . 20 …”

LDL receptor‐related protein 1 contributes to the clearance of the activated factor VII–antithrombin complex

“…Murine macrophages were derived from CD115 + cells obtained from macLRP1 + and macLRP1 − mice, as described previously . Cells were seeded at a density of 10 5 cells on sterile coverslips in 24‐well plates, in growth factor‐enriched RPMI‐1640 medium . The culture medium was changed every 2 days, and differentiation lasted for 6 days.…”

“…Following differentiation, all cells were positive for the macrophage markers CD206, CD163, and major histocompatibility complex class II. Human macrophages were derived from THP1 cells (American Type Culture Collection Manassas, VA, USA), with a previously established differentiation protocol .…”

Recognition of lipoproteins by scavenger receptor class A members

“…The scavenger receptor (SR) was first identified in late 1970s because of its binding with the modified low-density lipoproteins (LDLs) ( 1 ). Over the past decades, a large number of SRs have been found with wide tissue distributions and play important roles in maintaining homeostasis and host defense by recognizing both self- and non–self-ligands ( 2 , 3 , 4 ), including proteins, carbohydrates ( 5 , 6 ), and lipids ( 7 , 8 ), and they are also associated with many diseases ( 9 , 10 , 11 ) such as autoimmune diseases ( 12 ), cardiovascular diseases ( 11 , 13 , 14 ), and cancer ( 9 , 10 , 12 , 15 ).…”