Collaborative UVA research uncovers stages of lung cell regeneration

Macrophages are white blood cells that act as sentinels. They monitor tissue disturbances due to infection or injury, clean up dead cells and stimulate the action of other immune cells.

The researchers studied epithelial regeneration in two different species and from two different anatomical sources: mice with airway-injured lungs and zebrafish with severed tail fins. The study observed macrophage dependence on pannexin 1, sometimes abbreviated as Panx1, by isolating the protein from test subjects before experiments, through methods such as breeding and chemical suppression.

“These data identify a Panx1-mediated communication circuit between epithelial cells and macrophages as a key step in promoting epithelial regeneration after injury,” the research says.

The biological domino effect the scientists discovered, though complex, appears to work like this: Enzymes programmed to break down injured and dying cells activate pannexin 1, which opens a channel for a molecule that carries energy. This release of energy and other factors help regulate the type of macrophage produced. These specialized macrophages then induce the encoded gene that promotes cell proliferation.

“Understanding the mechanisms by which epithelial repair is achieved is essential to delineate novel targets that promote recovery after organ injury, particularly in the lungs where no existing therapy directly targets lung regeneration,” the paper states.

First author Christopher Lucas and corresponding author Kodi S. Ravichandran were joined on the article by UVA researchers Christopher B. Medina, Michael H. Raymond, Turan Tufan, J. Iker Etchegaray, Brady Barron, Sanja Arandjelovic, Eugene Ke, Emily Farber and Suna Onngut-Gumuscu.

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