Poised. Heregulin (red) and erbB2 (green) sit on different sides of epithelial cells until an injury spurs them to action.

Cellular Band-Aids

The body's first layer of defense against the world consists of epithelial cells like those found in the skin and lungs. Now scientists have discovered an elegantly simple mechanism that helps quickly repair injured lung tissue, preventing infection.

Researchers had already spotted the molecular response team in the lungs. After lung epithelial cells are damaged, a molecule called heregulin binds to another protein, erbB2. This binding stimulates new cells to grow and replace the injured ones. But airway epithelial cells contain both molecules at all times, so researchers wondered what keeps healthy tissues from growing out of control.

To find out, cell biologist Paola Vermeer of the University of Iowa in Iowa City and colleagues first examined donated human lung tissue. Applying antibodies that stick to heregulin and erbB2, they found that heregulin rests in the cell membrane on the side exposed to air, whereas erbB2 scatters only in the cell membrane facing other cells to the side and back.

Because airway epithelial cells are tightly connected, the researchers posited that the membrane proteins on opposite sides don't normally mix. When they mimicked physical damage to the epithelial layer, heregulin made its way to the other sides, activated erbB2, and stimulated cell growth. Lastly, the team showed that this whole process could be triggered by injuring the airways in rats. The team reports its findings in the 20 March issue of Nature. Now the researchers plan to investigate whether diseases such as bronchitis or cystic fibrosis are caused by the disruption of the two proteins' partitioning.

The result is "so beautifully simple," says cell biologist Keith Mostov at the University of California, San Francisco. Physical separation of the two proteins is an "easy-to-conceptualize mechanism by which airway epithelial cells are poised to heal themselves the moment they are injured." Additional research will show whether other epithelial cells such as skin also partake of this self-healing method.

Related site
Vermeer's adviser's site