MIT researchers find active new role for cell 'undertakers' in cell death


CAMBRIDGE, Mass. -- Certain cells previously thought to be merely undertakers are actually the Jack Kevorkians of the cell world, Massachusetts Institute of Technology researchers report in the July 12 issue of Nature.

The discovery could lead to drugs that kill cells that are incapable of apoptosis, or programmed cell death, such as cancer cells, or drugs that save cells that are slowly dying in stroke, heart attack or neurological disease victims.

The only role of phagocytes, or engulfing cells, was believed to be that of a clean-up crew that got rid of dying cells so harmful by-products wouldn't hurt the organism. But the MIT research team -- H. Robert Horvitz, MIT biology professor and Howard Hughes Medical Institute investigator; MIT biology graduate student Peter W. Reddien; and former MIT postdoctoral associate Scott Cameron -- found that phagocytes play a role in helping cells die.

In the past 15 years, Horvitz has discovered many of the genes controlling apoptosis in the nematode Caenorhabditis elegans. Similar genes exist in humans, and the researchers believe that the cell-death process involving engulfing cells may also exist in humans.

POISED BETWEEN LIFE AND DEATH

Programmed cell death -- in which healthy, normal cells kill themselves -- is a necessary part of shaping developing tissues and organs and refining the central nervous system.

It also is used by the body in immune cell development and function and for removing unnecessary or damaged cells.

Phagocytes are cells that engulf and ingest dying cells. In the human body, they are called macrophages.

"We propose that engulfment actively promotes the killing process rather than passively eliminates the opportunity for recovery," the authors write.

Drugs that inhibit engulfment in humans may help in situations in which cells are poised between survival and death, such as heart cells near tissue killed by a heart attack or in retinitis pigmentosa or in slow degenerative neurological diseases such as Lou Gehrig's disease or Alzheimer's disease.

SUICIDE OR MURDER?

The MIT researchers used a genetic mutation that eliminated the function of phagocytes and then examined cell death in neuronal and embryonic cells in the roundworm. They found that many cells died anyway, but some cells that had been programmed to die went on to survive and differentiate.

"We found that phagocytosis plays an active role in promoting programmed cell death," Reddien said. "This demonstrates that engulfing cells are involved in some way in the process of apoptosis.

"This will provide a new way of thinking about programmed cell death," he said. "There is a mechanism for promoting cell death by engulfing cells that needs to be investigated."

This work was supported by the National Science Foundation, the Howard Hughes Medical Institute, a Merck/MIT collaborative fellowship and a National Institutes of Health training grant.


Topics: Biology

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