Led by TSRI President Richard Lerner, Ph.D. and Associate Professor in the Department of Chemistry Paul Wentworth, Jr, Ph.D., who made the original discovery, the team has been slowly gathering evidence over the last few years that the human body produces the reactive gas--most famous as the ultraviolet ray-absorbing component of the ozone layer--as part of a mechanism to protect it from bacteria and fungi.
"Ozone was a big surprise," says TSRI Professor Bernard Babior, M.D., Ph.D. "But it seems that biological systems manufacture ozone, and that ozone has an effect on those biological systems."
Now, in an important development in this unfolding story, Babior, Wentworth, and their TSRI colleagues report in an upcoming issue of the journal Proceedings of the National Academy of Sciences that the ozone appears to be produced in a process involving human immune cells known as neutrophils and human immune proteins known as antibodies.
"It is a tremendously efficient chemical and biological process," says Wentworth, who adds that the presence of ozone in the human body may be linked to inflammation, and therefore this work may have tremendous ramifications for treating inflammatory diseases.
The Ozone Hole in Each One of Us
Ozone is a reactive form of oxygen that exists naturally as a trace gas in the atmosphere. It is perhaps best known for its crucial role absorbing ultraviolet radiation in the stratosphere, where it is concentrated in a so-called ozone layer, protecting life on earth from solar radiation. Ozone is also a familiar component of air in industrial and urban settings where the gas is a hazardous component of smog. However, ozone has never before been detected in biology.
Two years ago, Lerner and Wentworth demonstrated that antibodies are able to produce ozone and other chemical oxidants when they are fed a reactive form of oxygen called singlet oxygen. And late last year, Lerner, Wentworth, and Babior demonstrated that the oxidants produced by antibodies can destroy bacteria by poking holes in their cell walls.
This was a completely unexpected development, since for the last 100 years, immunologists believed that antibodies--proteins secreted into the blood by the immune system--acted only to recognize foreign pathogens and attract lethal "effector" immune cells to the site of infection.
Questions, Answers, and More Questions
The question still remained, however, as to how the antibodies were making the ozone. The TSRI team knew that in order to make the ozone and other highly reactive oxidants, the antibodies had to use a starting material known as singlet oxygen, a rare, excited form of oxygen.
Now Babior and Wentworth believe they have found where the singlet oxygen comes from--one of the effector immune cells called neutrophils which are little cellular factories that produce singlet oxygen and other oxidants. During an immune response, the neutrophils engulf and destroy bacteria and fungi by blasting them with these oxidants.
The work of the TSRI scientists suggests that the antibacterial effect of neutrophils is enhanced by antibodies. In addition to killing the bacteria themselves, the neutrophils feed singlet oxygen to the antibodies, which convert it into ozone, adding weapons to the assault.
"This is really something new, and there are a million questions [that follow]," says Babior. "What does the ozone do to the body's proteins and nucleic acids? Can neutrophils make ozone without the antibodies? Is ozone made by other cells? How long does ozone last in the body? And, most importantly, how will these discoveries help to cure disease?"
The research team continues to investigate.
The article, "Investigating antibody-catalyzed ozone generation by human neutrophils," is authored by Bernard M. Babior, Cindy Takeuchi, Julie Ruedi, Abel Gutierrez, and Paul Wentworth, Jr. The article will be available online this week at: www.pnas.org/cgi/doi/10.1073/pnas.0530251100, and it will be published in an upcoming issue of the journal Proceedings of the National Academy of Sciences.
The research was funded by the National Institutes of Health (NIH), through research grants and through a training grant; and by The Skaggs Institute for Chemical Biology.
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