title: Macrophage receptor SR-AI is crucial to maintain normal plasma levels of coagulation factor X.
abstract: 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.
authors.affiliation: Unité 1176 INSERM, Le Kremlin-Bicêtre, France; and Unité Mixte de Recherche S1176, Université Paris-Sud, Le Kremlin-Bicêtre, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Muczynski
authors.affiliation: Unité 1176 INSERM, Le Kremlin-Bicêtre, France; and Unité Mixte de Recherche S1176, Université Paris-Sud, Le Kremlin-Bicêtre, France.
authors.forename: Amine
authors.initials: A
authors.lastname: Bazaa
authors.affiliation: Unité 1176 INSERM, Le Kremlin-Bicêtre, France; and Unité Mixte de Recherche S1176, Université Paris-Sud, Le Kremlin-Bicêtre, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Loubière
authors.affiliation: Unité 1176 INSERM, Le Kremlin-Bicêtre, France; and Unité Mixte de Recherche S1176, Université Paris-Sud, Le Kremlin-Bicêtre, France.
authors.forename: Amélie
authors.initials: A
authors.lastname: Harel
authors.affiliation: Unité 1176 INSERM, Le Kremlin-Bicêtre, France; and Unité Mixte de Recherche S1176, Université Paris-Sud, Le Kremlin-Bicêtre, France.
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Cherel
authors.affiliation: Unité 1176 INSERM, Le Kremlin-Bicêtre, France; and Unité Mixte de Recherche S1176, Université Paris-Sud, Le Kremlin-Bicêtre, France.
authors.forename: Cécile V
authors.initials: CV
authors.lastname: Denis
authors.affiliation: Unité 1176 INSERM, Le Kremlin-Bicêtre, France; and Unité Mixte de Recherche S1176, Université Paris-Sud, Le Kremlin-Bicêtre, France.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Lenting
authors.affiliation: Unité 1176 INSERM, Le Kremlin-Bicêtre, France; and Unité Mixte de Recherche S1176, Université Paris-Sud, Le Kremlin-Bicêtre, France.
authors.forename: Olivier D
authors.initials: OD
authors.lastname: Christophe
mesh_terms: D000818:Animals; D001777:Blood Coagulation / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D005170:Factor X / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D008264:Macrophages / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009000:Monocytes / Q000378:metabolism / Q000502:physiology; D051117:Scavenger Receptors, Class A / Q000235:genetics / Q000502:physiology*
chemical_list: D051117:Scavenger Receptors, Class A; D005170:Factor X