Intact immune cells (left column) had disintegrated (right column) only 100 seconds after their explosion was triggered by adding a hormone. A cell’s plasma membrane (bottom row, yellow) started to rupture 60 seconds after the hormone was added.Credit: C. Chai et al./Cell
New-found immune cells called ‘ruptoblasts’ explode when triggered, ejecting toxic chemicals capable of delivering death to surrounding cells in just minutes. The cells’ discoverers say that this process, which they call ruptosis, seems to be a new form of cell death that differs considerably from other known types.
The findings1, which appear today in the journal Cell, “are very interesting and thought-provoking,” says Kristopher Sarosiek, a cell-death researcher at the Harvard T.H. Chan School of Public Health in Boston, Massachusetts, who was not involved in the research. Although other forms of cell death are similar, none are identical, he says, “making ruptosis a new phenomenon”.
Vanishing cells
The authors stumbled on the newly discovered cells while studying a species of planarian flatworm (Schmidtea mediterranea). Planarians have long been of interest to scientists owing to their amazing regenerative capabilities — a single planarian cut into many pieces can regrow into a new worm. Planarians lack immune molecules called antibodies, but they do mount a robust immune response against pathogens as they regenerate. Bo Wang, an organismal biologist at Stanford University in California, and his colleagues were interested in how these worms deal with immune challenges, and began studying the animals at a cellular level.
During early observations, the researchers were confused by what they saw under the microscope: cells that seemed to rapidly disappear, leaving a no-man’s land strewn with dead cells in their vicinity. After confirming that what they were seeing wasn’t an artefact, the team dubbed the vanishing cells ‘ruptoblasts’ and set about characterizing them.
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They found that ruptosis seems to be triggered by the protein activin — a widely-studied hormone that is associated with cell differentiation and immune signalling. When a ruptoblast detects activin, calcium derived from the cell’s inner stores rapidly accumulates along the cell’s cytoskeleton. This creates a strong calcium gradient between the inside and outside of the cell, which can cause the ruptoblasts to explode in less than two minutes after sensing activin.
In vitro, ruptosis of a single cell killed as many as 70 surrounding cells, such as those of bacterial, planarian and mammalian origin, including human cells. “The speed and the completeness of cell destruction was very surprising to us,” Wang said.
