Antibodies are the immune system's reconnaissance forces: scouts that seek out foreign antigens and summon the big guns to wipe them out. But evidence now indicates that antibodies may also be killers in their own right. A study published online today by Science finds that antibodies can produce highly active forms of oxygen, likely including ozone. These compounds not only can kill bacteria but may be a previously unknown method of promoting inflammatory and other immune responses.
Previous work by Paul Wentworth, Richard Lerner, and their colleagues at the Scripps Research Institute in La Jolla, California, showed that when antibodies are supplied with a reactive form of oxygen known as singlet oxygen, they can convert water to hydrogen peroxide--a well-known bacteria killer (ScienceNOW, 7 September 2001).
The team's new work suggests a surprising and novel twist in antibodies' modus operandi. The researchers demonstrated that antibodies can single-handedly kill bacteria. One set of test tube experiments demonstrated that antibodies armed with singlet oxygen wiped out more than 95% of Escherichia coli bacteria. But the experiments turned up a puzzle: The antibodies weren't generating enough hydrogen peroxide to account for all the dead cells. This fact suggested that some other, more powerful bactericidal agent was also being formed.
Additional experiments pointed to ozone as the most likely suspect. For example, the researchers found that antibodies provided with singlet oxygen produce an oxidizing agent that splits the dye indigo carmine, just as ozone does. But the work left one big question hanging: Is there a plausible physiological source of singlet oxygen? Apparently so. The team reports evidence that immune cells called neutrophils, which help destroy invading bacteria, can provide it.
In addition to showing that antibodies can generate hydrogen peroxide and ozone, the team linked this activity to an inflammatory response in living rats called the Arthus reaction, which is triggered by injecting antibodies into the animals' skin. Analysis of the inflamed skin tissue showed that it, too, contained an oxidizing agent that behaves just like ozone.
The work is "amazing," says chemist Chris Foote of the University of California, Los Angeles. It shows, he says, that "there's a powerful oxidant there that no one suspected." Such direct effects put antibodies in a whole new light, adds immunologist Carl Nathan of the Weill Cornell Medical Center in New York City.
--JEAN MARX
Related site
Richard Lerner's lab site
