Phagocytosis and clearance of apoptotic cells is mediated by MER

Rona S. Scott, Eileen J. McMahon, Shannon M. Pop, Elizabeth A. Reap, Roberto Caricchio, Philip L. Cohen, H. Shelton Earp and Glenn K. Matsushima ()
Additional contact information
Rona S. Scott: UNC Neuroscience Center
Eileen J. McMahon: Department of Microbiology and Immunology
Shannon M. Pop: Curriculum in Oral Biology
Elizabeth A. Reap: Alphavax Human Vaccines
Roberto Caricchio: University of Pennsylvania
Philip L. Cohen: University of Pennsylvania
H. Shelton Earp: Department of Pharmacology and Lineberger Comprehensive Cancer Center
Glenn K. Matsushima: UNC Neuroscience Center

Nature, 2001, vol. 411, issue 6834, 207-211

Abstract: Abstract Apoptosis is fundamental to the development and maintenance of animal tissues and the immune system1. Rapid clearance of apoptotic cells by macrophages is important to inhibit inflammation and autoimmune responses against intracellular antigens2,3,4. Here we report a new function for Mer, a member of the Axl/Mer/Tyro3 receptor tyrosine kinase family. merkd 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 merkd 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 merkd 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.

Date: 2001
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DOI: 10.1038/35075603

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