New gene-editing system enables large-scale studies of gene function.
Certain cells previously thought to be merely undertakers are actually the Jack Kevorkians of the cell world, MIT researchers reported in the July 12 issue of Nature.
The only role of phagocytes, or engulfing cells, was believed to be that of a cleanup crew that got rid of dying cells so harmful by-products wouldn't hurt the organism.
But the MIT research team of H. Robert Horvitz, professor of biology and a Howard Hughes Medical Institute investigator, biology graduate student Peter W. Reddien and former postdoctoral fellow Scott Cameron found that engulfing cells play a role in helping cells die.
In the past 15 years, Horvitz has discovered many of the genes controlling apoptosis, or programmed cell death, in the roundworm Caenorhabditis elegans. These studies have helped identify similar human genes that also control apoptosis.
The researchers suspect that the cell-killing process involving engulfing cells may also exist in humans.
If so, understanding this process may lead to drugs that kill cells that are incapable of apoptosis such as cancer cells, or save cells that are slowly dying in stroke, heart attack or neurological disease victims.
CELLS 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. The process 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. 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.
The researchers utilized a genetic mutation that eliminated the function of engulfing cells and 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 observation demonstrates that engulfing cells are involved in the process of apoptosis.
"Our discovery provides a new way of thinking about programmed cell death," he said. "In addition, 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.
A version of this article appeared in MIT Tech Talk on July 18, 2001.