Sliced. A zebrafish larvae tail 3 minutes, 17 minutes, and 61 minutes (top to bottom) after being cut. Hydrogen peroxide (red) emanates from the wound, fading to yellow and green as it dissipates through tissue.

Philipp Niethammer

Calling All White Blood Cells

Anyone who has felt the sting as hydrogen peroxide foams and fizzes on a scraped knee knows about the compound's antiseptic properties. But new research suggests that hydrogen peroxide does more than just kill microbes. It may also call for reinforcements, summoning an army of bacteria-fighting cells to cuts and wounds.

Punctured skin sets off a chain reaction of chemical signals that activates blood-clotting and attracts an array of immune cells to guard against intruding microbes. Some of these cells, known as leukocytes, or white blood cells, kill by initiating a "respiratory burst," which releases highly reactive antimicrobial molecules, including hydrogen peroxide produced by the body itself.

Biologist Philipp Niethammer, a postdoctoral researcher at Harvard Medical School in Boston, was trying to coax such a hydrogen peroxide burst out of a nicked zebrafish tail when he noticed something odd. "I saw something bursting at the wound," he says, "but I didn't see leukocytes there." That bursting, experiments revealed, was hydrogen peroxide--appearing an average of 17 minutes before the arrival of the white blood cells that are supposed to produce it. To Niethammer, it appeared as if hydrogen peroxide was bringing leukocytes to the wound rather than the other way around.

To confirm the theory, Niethammer and his colleagues bathed zebrafish larvae in compounds known to inhibit the production of hydrogen peroxide. When researchers nicked larvae tails in the presence of the inhibitors, leukocytes stayed away: An average of fewer than one per larvae appeared at the cut within 42 minutes, compared with four to six under normal conditions. Next, the team used genetic manipulation to pinpoint the enzyme responsible for producing hydrogen peroxide. The culprit, a protein known as duox, is also found in the thyroid, digestive tract, and lungs of humans. Asthma and other disorders result from excessive inflammation in these tissues, so duox may play a role in those conditions, the researchers report tomorrow in Nature.

Paul Martin, a cell biologist at the University of Bristol in the United Kingdom, says the work identifies a key time point in wound healing. "Now we know the first step," he says. So, can that brown drugstore bottle of hydrogen peroxide also bring leukocytes to a wound? That's an open question, says Niethammer. He's now investigating whether white blood cells detect hydrogen peroxide directly or whether the compound is part of a longer signaling chain.