Phagocytosis and Clearance of Apoptotic Cells Is Mediated by MER

Nature. 2001 May 10;411(6834):207-11. doi: 10.1038/35075603.

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.

MeSH terms

  • 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
  • Macrophages, Peritoneal / immunology*
  • Macrophages, Peritoneal / metabolism
  • Macrophages, Peritoneal / ultrastructure
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Microscopy, Electron, Scanning
  • Microspheres
  • Mutation / genetics
  • Phagocytosis*
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Radiation Chimera / immunology
  • Receptor Protein-Tyrosine Kinases*
  • Receptors, Fc / immunology
  • Thymus Gland / cytology*
  • Thymus Gland / drug effects
  • Thymus Gland / immunology
  • Thymus Gland / ultrastructure
  • c-Mer Tyrosine Kinase

Substances

  • Antibodies, Antinuclear
  • Proto-Oncogene Proteins
  • Receptors, Fc
  • Cytochalasin B
  • Dexamethasone
  • Mertk protein, mouse
  • Protein-Tyrosine Kinases
  • Receptor Protein-Tyrosine Kinases
  • c-Mer Tyrosine Kinase