In mammals, cells that undergo apoptosis are marked for degradation by macrophages with phosphatidylserine. Hanayama et al. (see the Perspective by Züllig and Hengartner) report the phenotype of mice lacking milk fat globule EGF factor-8 (MFG-E8), a protein secreted by macrophages that binds to apoptotic cells and appears to promote their engulfment. The knockout mice showed engulfment defects; in particular, uptake of apoptotic lymphocytes by macrophages in germinal centers of the immune system was compromised. The animals also had enlarged spleens and signs of autoimmune disease.
R. Hanayama, M. Tanaka, K. Miyasaka, K. Aozasa, M. Koike, Y. Uchiyama, S. Nagata, Autoimmune disease and impaired uptake of apoptotic cells in MFG-E8-deficient mice. Science 304, 1147-1150 (2004). [Abstract] [Full Text]