References
Query Results -- Details
MGI Accession ID: MGI:3794789
J Number: J:135906
Other Accession IDs:
Title: Lactadherin deficiency leads to apoptotic cell accumulation and accelerated atherosclerosis in mice.
Authors: Ait-Oufella H; Kinugawa K; Zoll J; Simon T; Boddaert J; Heeneman S; Blanc-Brude O; Barateau V; Potteaux S; Merval R; Esposito B; Teissier E; Daemen MJ; Leseche G; Boulanger C; Tedgui A; Mallat Z
Journal: Circulation
Volume: 115
Issue: 16
Date: 2007 Apr 24
Year: 2007
Pages: 2168-77
Review Status: Peer Reviewed
Abstract:
BACKGROUND: Atherosclerosis is an immunoinflammatory disease; however, the key factors responsible for the maintenance of immune regulation in a proinflammatory milieu are poorly understood. METHODS AND RESULTS: Here, we show that milk fat globule-EGF factor 8 (Mfge8, also known as lactadherin) is expressed in normal and atherosclerotic human arteries and is involved in phagocytic clearance of apoptotic cells by peritoneal macrophages. Disruption of bone marrow-derived Mfge8 in a murine model of atherosclerosis leads to substantial accumulation of apoptotic debris both systemically and within the developing lipid lesions. The accumulation of apoptotic material is associated with a reduction in interleukin-10 in the spleen but an increase in interferon-gamma production in both the spleen and the atherosclerotic arteries. In addition, we report a dendritic cell-dependent alteration of natural regulatory T-cell function in the absence of Mfge8. These events are associated with a marked acceleration of atherosclerosis. CONCLUSIONS: Lack of Mfge8 in bone marrow-derived cells enhances the accumulation of apoptotic cell corpses in atherosclerosis and alters the protective immune response, which leads to an acceleration of plaque development.
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