New molecular key to disposal of dying cells

CHAPEL HILL - Along with derailing the body's rapid disposal of dying cells, defective functioning of a gene identified at the University of North Carolina at Chapel Hill also may contribute to tissue inflammation and the development of autoimmune diseases such as systemic lupus erythematosus.

A report of the new findings appears in the May 10 issue of Nature, the international science journal.

The report focuses on the function of a gene called Mer, which is expressed as a receptor on monocytes and macrophages, scavenger cell that circulate throughout the body or reside in tissue and ingest dead tissue and degenerated cells. Together with the genes Axl and Tyro3, Mer comprises a family of molecules known as receptor tyrosine kinases, which serve multiple functions in different tissues.

Scientists at the UNC School of Medicine's Lineberger Comprehensive Cancer Center led by director H. Shelton Earp III, MD cloned human and mouse Mer in 1995. This achievement led to their development of a Mer knockout mouse, a strain of mice defective in Mer function, which would provide insights to the function of Mer.

UNC researchers have been studying the role of Mer in cancer development because Mer, like Axl, is found on cancer cells. After further study, it appears that Mer is also an important player in phagocytosis, the rapid clearance from tissue of dying, or apoptotic, cells. Phagocytosis of other particles and bacteria occur by other mechanisms independent of Mer.

"This paper details the knockout mouse research and describes the basic mechanisms involved in the clearing of apoptotic cells particularly by macrophages," said study co-author Glenn K. Matsushima, PhD, a molecular neuroimmunologist at the UNC Neuroscience Center. "We show that mutating this receptor prohibits the ingestion of apoptotic cells."

In the study led by Rona S. Scott, PhD, of Matushima's lab, thymus cells that had been made apoptotic by treatment with the corticosteroid de

Contact: Leslie H. Lang
University of North Carolina School of Medicine

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