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Macrophages from patients affected by Lysinuric Protein Intolerance (LPI) exhibit an impaired phagocytosis
Author(s) -
Rotoli Bianca Maria,
Barilli Amelia,
Visigalli Rossana,
DallˈAsta Valeria
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1034.2
Subject(s) - phagocytosis , immune system , macrophage , monocyte , internalization , biology , amino acid , microbiology and biotechnology , immunology , chemistry , biochemistry , in vitro , cell
Lysinuric Protein Intolerance (LPI) is a recessive aminoaciduria caused by defective cationic amino acid transport in epithelial cells of intestine and kidney. SLC7A7, the gene mutated in LPI, codifies for the y+LAT1 subunit of system y + L amino acid transporter. LPI patients frequently display severe complications, such as pulmonary disease, haematological abnormalities and disorders of the immune response, that can not be explained by the transport defect. Aim of the study is to investigate the consequences of SLC7A7 mutations on specific macrophage functions, so as to elucidate the role of macrophage dysfunction in the development of pulmonary and immunological complications of LPI. Peripheral blood monocytes were isolated from 3 LPI patients and 5 normal healthy donors and cultured for 7 days in the presence of GM‐CSF so as to obtain monocyte‐derived macrophages (MDM). System y + L activity appears markedly compromised in LPI monocytes and macrophages, as measured both as an influx or efflux route of 3 H‐arginine. Moreover, LPI macrophages display a significant impairment of the phagocytic activity, detected by the internalization of fluorescent latex beads. These results demonstrate that SLC7A7/y+LAT1 mutations lead to a defective phenotype of macrophages, supporting the pathogenetic role of these cells in the development of LPI‐associated complications.