Macrophage uptake and accumulation of folates are polarization-dependent in vitro and in vivo and are regulated by activin A.

Abstract:

:Vitamin B9, commonly known as folate, is an essential cofactor for one-carbon metabolism that enters cells through three major specialized transporter molecules (RFC, FR, and PCFT), which differ in expression pattern, affinity for substrate, and ligand-binding pH dependency. We now report that the expression of the folate transporters differs between macrophage subtypes and explains the higher accumulation of 5-MTHF-the major folate form found in serum-in M2 macrophages in vitro and in vivo. M1 macrophages display a higher expression of RFC, whereas FRβ and PCFT are preferentially expressed by anti-inflammatory and homeostatic M2 macrophages. These differences are also seen in macrophages from normal tissues involved in folate transit (placenta, liver, colon) and inflamed tissues (ulcerative colitis, RA), as M2-like macrophages from normal tissues express FRβ and PCFT, whereas TNF-α-expressing M1 macrophages from inflamed tissues are RFC+. Besides, we provide evidences that activin A is a critical factor controlling the set of folate transporters in macrophages, as it down-regulates FRβ, up-regulates RFC expression, and modulates 5-MTHF uptake. All of these experiments support the notion that folate handling is dependent on the stage of macrophage polarization.

journal_name

J Leukoc Biol

authors

Samaniego R,Palacios BS,Domiguez-Soto Á,Vidal C,Salas A,Matsuyama T,Sánchez-Torres C,de la Torre I,Miranda-Carús ME,Sánchez-Mateos P,Puig-Kröger A

doi

10.1189/jlb.0613345

subject

Has Abstract

pub_date

2014-05-01 00:00:00

pages

797-808

issue

5

eissn

0741-5400

issn

1938-3673

pii

jlb.0613345

journal_volume

95

pub_type

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