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.

journal_name

Blood

journal_title

Blood

authors

Muczynski V,Bazaa A,Loubière C,Harel A,Cherel G,Denis CV,Lenting PJ,Christophe OD

doi

10.1182/blood-2015-05-647032

subject

Has Abstract

pub_date

2016-02-11 00:00:00

pages

778-86

issue

6

eissn

0006-4971

issn

1528-0020

pii

blood-2015-05-647032

journal_volume

127

pub_type

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