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

作者：Samaniego Rafael; Soler Palacios Blanca; Domiguez Soto Angeles; Vidal Carlos; Salas Azucena; Matsuyama Takami; Sanchez Torres Carmen; de la Torre Inmaculada; Eugenia Miranda Carus Maria; Sanchez Mateos Paloma; Puig Kroeger Amaya^*

来源：Journal of Leukocyte Biology, 2014, 95(5): 797-808.

DOI：10.1189/jlb.0613345

• folate metabolism
• macrophage metabolism
• folate transporters
• folate receptor beta

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 FR beta 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 FR beta and PCFT, whereas TNF-alpha-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 FR beta, 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. %26lt;br%26gt;Folate handling is dependent on the macrophage polarization state, where folate metabolism could provide useful diagnostic or therapeutic markers for inflammatory pathologies.

• 出版日期2014-5