Phagocytosis and clearance of apoptotic cells is mediated by MER

Apoptosis is fundamental to the development and maintenance of animal tissu es and the immune system(1). Rapid clearance of apoptotic cells by macropha ges is important to inhibit inflammation and autoimmune responses against i ntracellular antigens(2-4). Here we report a new function for Mer, a member of the Axl/Mer/ Tyro3 receptor tyrosine kinase family. mer(kd) mice with a cytoplasmic truncation of Mer had macrophages deficient in the clearance o f apoptotic thymocytes. This was corrected in chimaeric mice reconstituted with bone marrow from wild-type animals. Primary macrophages isolated from mer(kd) mice showed that the phagocytic deficiency was restricted to apopto tic cells and was independent of Fc receptor-mediated phagocytosis or inges tion of other particles. The inability to clear apoptotic cells adequately may be linked to an increased number of nuclear autoantibodies in mer(kd) m ice. Thus, the Mer receptor tyrosine kinase seems to be critical for the en gulfment and efficient clearance of apoptotic cells. This has implications for inflammation and autoimmune diseases such as systemic lupus erythematos us.