title: Arginine transport is impaired in C57Bl/6 mouse macrophages as a result of a deletion in the promoter of Slc7a2 (CAT2), and susceptibility to Leishmania infection is reduced.
abstract: Host genetic factors play a crucial role in immune response. To determine whether the differences between C57Bl/6 and BALB-C mice are due only to the production of cytokines by T-helper 1 cells or T-helper 2 cells, we obtained bone marrow-derived macrophages from both strains and incubated them with these cytokines. Although the induction of Nos2 and Arg1 was similar in the 2 strains, infectivity to Leishmania major differed, as did macrophage uptake of arginine, which was higher in BALB-C macrophages. The levels of interferon γ- and interleukin 4-dependent induction of the cationic amino acid transporter SLC7A2 (also known as "cationic amino acid transporter 2," or "CAT2") were decreased in macrophages from C57Bl/6 mice. This reduction was a result of a deletion in the promoter of one of the 4 AGGG repeats. These results demonstrate that the availability of arginine controls critical aspects of macrophage activation and reveal a factor for susceptibility to Leishmania infection.
authors: Macrophage Biology Group, Department of Physiology and Immunology, Universitat de Barcelona, Spain.
authors: M Gloria
authors: MG
authors: Sans-Fons
authors: Andrée
authors: A
authors: Yeramian
authors: Selma
authors: S
authors: Pereira-Lopes
authors: Luis F
authors: LF
authors: Santamaría-Babi
authors: Manuel
authors: M
authors: Modolell
authors: Jorge
authors: J
authors: Lloberas
authors: Antonio
authors: A
authors: Celada
mesh_terms: D026923:Amino Acid Transport Systems, Basic / Q000235:genetics*; D000818:Animals; D001120:Arginine / Q000378:metabolism*; D001692:Biological Transport; D002478:Cells, Cultured; D060467:Disease Resistance; D018320:Leishmania major / Q000276:immunology*; D007896:Leishmaniasis / Q000235:genetics*; D008264:Macrophages / Q000378:metabolism* / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011401:Promoter Regions, Genetic; D017384:Sequence Deletion
chemical_list: D026923:Amino Acid Transport Systems, Basic; C087435:Slc7a2 protein, mouse; D001120:Arginine