Phagocytosis and clearance of apoptotic cells is mediated by MER.

Abstract	Apoptosis is fundamental to the development and maintenance of animal tissues and the immune system. Rapid clearance of apoptotic cells by macrophages is important to inhibit inflammation and autoimmune responses against intracellular antigens. 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 of 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 apoptotic cells and was independent of Fc receptor-mediated phagocytosis or ingestion of other particles. The inability to clear apoptotic cells adequately may be linked to an increased number of nuclear autoantibodies in mer(kd) mice. Thus, the Mer receptor tyrosine kinase seems to be critical for the engulfment and efficient clearance of apoptotic cells. This has implications for inflammation and autoimmune diseases such as systemic lupus erythematosus.
Authors	R S Scott, E J McMahon, S M Pop, E A Reap, R Caricchio, P L Cohen, H S Earp, G K Matsushima
Journal	Nature (Nature) Vol. 411 Issue 6834 Pg. 207-11 (May 10 2001) ISSN: 0028-0836 [Print] England
PMID	11346799 (Publication Type: Journal Article)
Chemical References	Antibodies, Antinuclear Proto-Oncogene Proteins Receptors, Fc Cytochalasin B Dexamethasone Mertk protein, mouse Protein-Tyrosine Kinases Receptor Protein-Tyrosine Kinases c-Mer Tyrosine Kinase
Topics	Animals Antibodies, Antinuclear (immunology) Apoptosis (drug effects) Bone Marrow Transplantation Cell Adhesion Cells, Cultured Crosses, Genetic Cytochalasin B (pharmacology) Dexamethasone (pharmacology) Female Flow Cytometry Immunohistochemistry Listeria monocytogenes (immunology) Macrophages, Peritoneal (cytology, immunology, metabolism, ultrastructure) Male Mice Mice, Inbred C57BL Mice, Mutant Strains Microscopy, Electron, Scanning Microspheres Mutation (genetics) Phagocytosis Protein-Tyrosine Kinases (genetics, metabolism) Proto-Oncogene Proteins (genetics, metabolism) Radiation Chimera (immunology) Receptor Protein-Tyrosine Kinases Receptors, Fc (immunology) Thymus Gland (cytology, drug effects, immunology, ultrastructure) c-Mer Tyrosine Kinase

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