Bang! Exploding immune cells splatter potent toxins everywhere
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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<br>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.<br>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”.<br>Vanishing cells<br>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.<br>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.<br>The hunt for the next CRISPR: how warring microbes are inspiring new technology
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.<br>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.<br>A new way to die<br>There are a variety of ways in which cells can perish, and ruptosis seems to be distinct from these. In a pre-programmed process called apoptosis, for example, cells are gradually demolished, helping to keep tissues healthy. Other cells die from an internal build-up of iron, a process called ferroptosis. Unlike ruptosis, these processes tend to require direct contact between cells or they take hours to induce. But Sarosiek notes that ruptosis does bear some resemblance to a form of cell death called pyroptosis, in which immune cells detect pathogens or damage and split, spilling pro-inflammatory compounds.<br>What were the first animals? The fierce sponge–jelly battle that just won’t end
The identity of the cell-killing compound in ruptoblasts is not yet clear, although preliminary evidence suggests that it’s likely to be a protein of modest size. When the cells were mechanically ruptured by the scientists in an activin-free environment, they did not annihilate surrounding cells, suggesting that the activin changes something inside the ruptoblasts.<br>As well as trying to identify the toxic agent, the team is looking for evidence of ruptoblasts in other organisms. The researchers found genetic markers for ruptoblast-like cells in other ‘bilaterians’ — animals that have bilateral symmetry — such as other flatworms and worms in the annelid group, which includes earthworms. The findings suggest that ruptoblasts are ancient in origin and conserved across basal bilaterians, a group that includes many regenerating species. This link has given the team a new working hypothesis.<br>“We think the cells are tolerated by planarians and other...