Ozone is Produced by Antibodies During Bacterial Killing
- The Scripps Research Institute
La Jolla, California
November 14, 2002:
Professor Richard A. Lerner, M.D., Associate Professor Paul Wentworth, Jr., Ph.D., and a team of
investigators at The Scripps Research Institute (TSRI)
is reporting that antibodies can destroy bacteria, playing a hitherto
unknown role in immune protection. Furthermore, the team found that when
antibodies do this, they appear to produce the reactive gas ozone.
"Ozone has never been considered a part of biology before," says
Lerner, who is Lita Annenberg Hazen Professor of Immunochemistry and
holds the Cecil H. and Ida M. Green Chair in Chemistry at TSRI. The
report will appear in an upcoming issue of the journal Science.
The ozone may be part of a previously unrecognized killing mechanism
that would enhance the defensive role of antibodies by allowing them
to participate directly in the killing. Previously, antibodies were
believed only to signal an immune response.
Also called immunoglobulins, antibodies are secreted proteins
produced by immune cells that are designed to recognize a wide range
of foreign pathogens. After a bacterium, virus, or other pathogen
enters the bloodstream, antibodies target antigens [proteins, fat
molecules, and other pieces of the pathogen] that are specific to that
foreign invader. These antibodies then alert the immune system to the
presence of the invaders and attract lethal "effector" immune cells
to the site of infection.
For the last hundred years, immunologists have firmly held that the
role of antibodies was solely to recognize pathogens and signal the
immune system to make an immune response. The conventional wisdom
was that the dirty work of killing the pathogens was to be left to
other parts of the immune system.
Now, Lerner, Wentworth and their colleagues have demonstrated that
antibodies also have the ability to kill bacteria. This suggests
that rather than simply recognizing foreign antigens and then
activating other parts of the immune system to the site of
infection, the antibodies may further enhance the immune response by
directly killing some of the bacteria themselves.
Lerner, Wentworth, and their colleagues found that antibodies appear to
make ozone, which they detected through its chemical signature, which no
other known molecule has. Never before has ozone been detected in
It has been known that all antibodies have the ability to produce
hydrogen peroxide, but they need to first have available a molecule
known as "singlet" oxygen - another highly reactive oxygen species -
to use as a substrate.
Singlet oxygen is an energetically charged form of oxygen that
forms spontaneously during normal metabolic processes. Phagocytes
like neutrophils produce singlet oxygen and are the most likely
source of the substrate for antibody production of hydrogen peroxide.
Antibodies attract neutophils to the site of an infection.
Once there, the neutrophils will engulf and destroy bacteria and
other pathogens by blasting them with singlet oxygen and other
oxidative molecules. The antibodies combine singlet oxygen with
water to produce hydrogen peroxide, producing ozone as a side product.
Another interesting finding is that the antibodies carry the
reaction through an unusual intermediate chemical species of dihydrogen trioxide, a reduced form
Dihydrogen trioxide has also never before been observed in biological
systems, and its presence as an intermediate has been the source of considerable speculation in
the scientific community.
The team's reported detection of ozone is strong support of this
proposed dihydrogen trioxide intermediate, and now the team is
tackling the larger question of what it means.
The research article, "Evidence for Antibody-Catalyzed Ozone
Formation in Bacterial Killing" is authored by Paul Wentworth, Jr.,
Jonathan E. McDunn, Anita D. Wentworth, Cindy Takeuchi, Jorge Nieva,
Teresa Jones, Cristina Bautista, Julie M. Ruedi, Abel Gutierrez, Kim
D. Janda, Bernard M. Babior, Albert Eschenmoser, and Richard A. Lerner,
and appears in the November 18, 2002 "Science Express," the advanced publication edition of the
journal Science. The article will appear in
Science later this year.
-Edited for ozonetherapy by Dr. Saul Pressman