| First Author | Ait-Oufella H | Year | 2007 |
| Journal | Circulation | Volume | 115 |
| Issue | 16 | Pages | 2168-77 |
| PubMed ID | 17420351 | Mgi Jnum | J:135906 |
| Mgi Id | MGI:3794789 | Doi | 10.1161/CIRCULATIONAHA.106.662080 |
| Citation | Ait-Oufella H, et al. (2007) Lactadherin deficiency leads to apoptotic cell accumulation and accelerated atherosclerosis in mice. Circulation 115(16):2168-77 |
| abstractText | 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. |
