Neutrophils Coast to Coast
By Jason Socrates
Bardi
To borrow a phrase from Thomas Hobbes, the lives of neutrophils
are nasty, brutish, and short.
But unlike Hobbes' assessment of the life of man, the nasty,
brutish, and short life of active neutrophils is a positive
thing—for these are qualities that let them destroy bacteria
and help us survive in a world filled with pathogens.
Our first line of defense against invading pathogens, neutrophils
are the most common white blood cell in circulation. Their
average life span is but a few hours in the bloodstream. After
this, they move into the tissues to search out bacteria and
fungi, which they kill with highly reactive oxidizing agents
and toxic proteins.
"Neutrophils are very small cells, but they are very nasty
microbicidal agents," says Bernard Babior, professor at The
Scripps Research Institute (TSRI) and an expert in neutrohils,
which he has been studying for over 30 years. "An active neutrophil
kills a bacterium in only a few seconds, using at least a
dozen and a half mechanisms."
It is a good thing that neutrophils do what they do, because
they are essential for life.
A Fish to Water
Babior's research on neutrophils has taken him from East
Coast to West Coast and resulted in numerous honors, awards,
and memberships in top scientific societies, including the
National Academy of Sciences, to which he was elected in 1999.
He first began studying neutrophils in the early 1970s,
when he was a faculty member at Harvard Medical School, a
few years after finishing his Ph.D. with 1964 Nobel laureate
Konrad Bloch. Babior pioneered research on the NAD(P)H oxidase
and discovered that neutrophils produce superoxide, a discovery
that opened a field of research now involving many types of
cells and engaging the activities of laboratories around the
world.
Shortly after these experiments, he moved within the Boston
area to The New England Medical Center Hospital, where he
worked for over a decade before coming to TSRI in the mid-1980s.
Having grown up and attended college in Los Angeles and
having earned his medical degree at the University of California,
San Francisco, Babior was delighted to be back on the West
Coast. He still remembers the day he arrived—February
1, 1986.
"I was like a fish diving back into water," he says. "I
love it here."
At TSRI, Babior continued his work on the oxidase. In addition,
he has become involved in research on a related question that
has produced some highly unusual results.
Neutrophils May be Ozone Factories
In a first for biology, TSRI President Richard Lerner and
associates demonstrated two years ago that antibodies are
able to produce ozone and other chemical oxidants when they
are fed a reactive form of oxygen called singlet oxygen.
Ozone, which had never before been observed in biological
systems, is a form of oxygen that exists naturally as a trace
gas in the atmosphere. It is perhaps best known for its crucial
role of absorbing ultraviolet radiation in the stratosphere,
where it is concentrated in the 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 had never
before been detected in biology.
That is, until late last year, when Lerner and Paul Wentworth,
Jr. demonstrated that ozone was produced by antibodies and
could destroy bacteria by poking holes in their cells 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.
The team has been slowly gathering evidence over the last
few years that the human body produces the reactive gas as
part of a mechanism to protect it from bacteria and fungi.
"Ozone was a big surprise," says Babior. "But it seems that
biological systems manufacture ozone, and that ozone has an
effect on those biological systems."
Neutrophils Potentially the Source of Singlet Oxygen
The question still remained, however, as to how the antibodies
were making the ozone. Lerner and Wentworth 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.
The question then became: What is the natural source of
singlet oxygen in the body?
Babior, with his years of experience working with neutrophils,
began collaborating with Lerner and Wentworth to investigate
whether neutrophils could be a source of singlet oxygen that
is required for ozone production.
Now, Babior, Wentworth, and TSRI colleagues are reporting
in an upcoming issue of the journal Proceedings of the
National Academy of Sciences that, indeed, the ozone appears
to be produced in a process involving neutrophils and antibodies.
This work 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 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 continues.
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