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Cell-Assisted Suicide

New role for “undertaker” cells may lead to new therapies.

Certain cells previously thought to be merely undertakers are actually the Kevorkians of the cell world because they help cells commit suicide, MIT researchers report in the July 12 issue of Nature.

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

These phagocytes, or engulfing cells, were believed to be no more than a clean-up crew that disposed of dying cells so that harmful by-products wouldn’t hurt the organism. But the MIT research team, led by H. Robert Horvitz, Peter Reddien and Scott Cameron, found that phagocytes actually play a role in helping cells die.

During the last 15 years, Horvitz has discovered many of the genes controlling apoptosis in the nematode Caenorhabditis elegans, a type of parasitic roundworm. 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

In mammals, 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. The body also uses it in immune cell development and function and for removing unnecessary or damaged cells. Phagocytes (called macrophages in the human body) are cells that engulf and ingest dying cells.

“We propose that engulfment actively promotes the killing process rather than passively eliminates the opportunity for recovery,” the authors write. “Engulfing cells promote the suicides of many and possibly all cells triggered to initiate programmed cell death.”

Drugs that inhibit this 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 or Alzheimer’s.

Suicide, Murder, or a Little of Both?

The researchers used a genetic mutation that eliminated the function of engulfing cells 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 says. “This demonstrates that engulfing cells are involved in some way in the process of apoptosis, possibly by signaling to activate the suicide mechanism.”

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