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Hydrogen peroxide marshals immune system
June 04, 2009When you were a kid your mom poured it on your scraped finger to stave off infection. When you got older you might have even used it to bleach your hair. Now there's another possible function for this over-the-counter colorless liquid: your body might be using hydrogen peroxide as an envoy that marshals troops of healing cells to wounded tissue.
Using the zebrafish as an animal model, researchers in the lab of Harvard Medical School professor of systems biology Timothy Mitchison and Dana Farber Cancer Institute professor Thomas Look have discovered that when the tail fins of these creatures are injured, a burst of hydrogen peroxide is released from the wound and into the surrounding tissue. Teams of rescue-working white blood cells respond to this chemical herald, crawl to the site of damage, and get to work.
"We've known for quite some time that when the body is wounded, white blood cells show up, and it's really a spectacular piece of biology because these cells detect the wound at some distance," says Mitchison. "But we haven't known what they're responding to. We do know something about what summons white blood cells to areas that are chronically inflamed, but in the case of an isolated physical wound, we haven't really known what the signal is."
These findings are reported in the June 4 issue of the journal Nature.
Philipp Niethammer, a postdoc in Mitchison's lab, and Clemmens Grabber, a postdoc in Look's lab, initiated this research project with no interest in wound healing. Rather, they were studying a groups of molecules called reactive oxygen species, or ROS. These small oxygen-derived molecules, of which hydrogen peroxide is one, have the potential to be both helpful and hurtful. Niethammer and Grabber were simply curious to find ways to detect ROS molecules in an organism.
To do this, they took a gene engineered to change color in the presence of hydrogen peroxide and inserted it into zebrafish embryos. Once the embryos entered the larvae stage after a few days, this synthetic gene spread throughout the entire body, essentially "wiring" the fish so that any discreet location in which hydrogen peroxide appears would glow.
But how do you coax the fish to produce a reactive chemical like hydrogen peroxide in the first place?
Since white blood cells have long been known to produce hydrogen peroxide, one obvious way to initiate chemical production would be to inflict a small wound onto the fish, and then, using microscopy, observe patterns of this chemical as white blood cells gathered around the wound. But much to the researchers surprise, they found that hydrogen peroxide immediately appeared at the wound site, prior to the arrival of any white blood cell, and quickly disseminated into neighboring tissue.
They repeated the experiment, this time in zebrafish where they'd disabled a protein that was previously discovered to produce hydrogen peroxide in the human thyroid gland. Not only did hydrogen peroxide not appear at the wound site, but white blood cells failed to respond to the injury.
"This was our real eureka! moment," says Niethammer. "We weren't too surprised that we could block hydrogen peroxide production through this technique, but what we didn't expect at all was that white blood cells wouldn't respond. This proved that the white blood cells needed hydrogen peroxide to sense the wound, and move towards it."
Of course, zebrafish are not people, and while our genomes share many similarities with these tiny fish, it isn't yet clear that natural selection has conserved this process throughout the evolutionary family tree. Still, these findings offer something of a conceptual shift in how to view human conditions where hydrogen peroxide plays a role.
"When we look at how hydrogen peroxide works in people, this really starts getting intriguing," says Mitchison.
In the human body, hydrogen peroxide is produced primarily in three places: lung, gut, and thyroid gland. Because hydrogen peroxide, and the proteins responsible for producing other ROS molecules, are especially present in lung and gut, the researchers hypothesize that human diseases relevant to these findings would include any in the lung and gut that involve disproportionate levels of white blood cells, like asthma, chronic pulmonary obstruction, and some inflammatory gut diseases.
"Our lungs are supposed to be sterile; our guts are anything but," says Mitchison. "It's very logical that both those tissues produce hydrogen peroxide all the time. Perhaps in conditions like asthma, the lung epithelia is producing too much hydrogen peroxide because it's chronically irritated, which, if our findings translate to humans, would explain inappropriate levels of white blood cells. This is certainly a question worth pursuing."
Mitchison is currently laying the groundwork for investigating this hypothesis.
Harvard Medical School
These findings are reported in the June 4 issue of the journal Nature.
Philipp Niethammer, a postdoc in Mitchison's lab, and Clemmens Grabber, a postdoc in Look's lab, initiated this research project with no interest in wound healing. Rather, they were studying a groups of molecules called reactive oxygen species, or ROS. These small oxygen-derived molecules, of which hydrogen peroxide is one, have the potential to be both helpful and hurtful. Niethammer and Grabber were simply curious to find ways to detect ROS molecules in an organism.
To do this, they took a gene engineered to change color in the presence of hydrogen peroxide and inserted it into zebrafish embryos. Once the embryos entered the larvae stage after a few days, this synthetic gene spread throughout the entire body, essentially "wiring" the fish so that any discreet location in which hydrogen peroxide appears would glow.
But how do you coax the fish to produce a reactive chemical like hydrogen peroxide in the first place?
Since white blood cells have long been known to produce hydrogen peroxide, one obvious way to initiate chemical production would be to inflict a small wound onto the fish, and then, using microscopy, observe patterns of this chemical as white blood cells gathered around the wound. But much to the researchers surprise, they found that hydrogen peroxide immediately appeared at the wound site, prior to the arrival of any white blood cell, and quickly disseminated into neighboring tissue.
They repeated the experiment, this time in zebrafish where they'd disabled a protein that was previously discovered to produce hydrogen peroxide in the human thyroid gland. Not only did hydrogen peroxide not appear at the wound site, but white blood cells failed to respond to the injury.
"This was our real eureka! moment," says Niethammer. "We weren't too surprised that we could block hydrogen peroxide production through this technique, but what we didn't expect at all was that white blood cells wouldn't respond. This proved that the white blood cells needed hydrogen peroxide to sense the wound, and move towards it."
Of course, zebrafish are not people, and while our genomes share many similarities with these tiny fish, it isn't yet clear that natural selection has conserved this process throughout the evolutionary family tree. Still, these findings offer something of a conceptual shift in how to view human conditions where hydrogen peroxide plays a role.
"When we look at how hydrogen peroxide works in people, this really starts getting intriguing," says Mitchison.
In the human body, hydrogen peroxide is produced primarily in three places: lung, gut, and thyroid gland. Because hydrogen peroxide, and the proteins responsible for producing other ROS molecules, are especially present in lung and gut, the researchers hypothesize that human diseases relevant to these findings would include any in the lung and gut that involve disproportionate levels of white blood cells, like asthma, chronic pulmonary obstruction, and some inflammatory gut diseases.
"Our lungs are supposed to be sterile; our guts are anything but," says Mitchison. "It's very logical that both those tissues produce hydrogen peroxide all the time. Perhaps in conditions like asthma, the lung epithelia is producing too much hydrogen peroxide because it's chronically irritated, which, if our findings translate to humans, would explain inappropriate levels of white blood cells. This is certainly a question worth pursuing."
Mitchison is currently laying the groundwork for investigating this hypothesis.
Harvard Medical School
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HYDROGEN PEROXIDE ANTISEPTIC SOLUTION 16 OZ by VI-JON/CUMBERLAND SWAN First Aid Antiseptic, oral debriding agent. For treatment of minor cuts and abrasions or for use as a gargle or mouth rinse. Helps prevent the risk of infection in cuts, scrapes and burns. Aids in the removal of phlegm, mucus or other secretions associated with occassional sore mouth. Contains 3% hydrogen peroxide. 16 fl oz. bottle. |
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Hydrogen Peroxide 12% 16 Ounces by O. W. Bionics H2O2 - Hydrogen Peroxide 16 fl. oz. Liquid by O-W & Company Hydrogen Peroxide (12%) that is food grade to be diluted with water and taken orally in an oxygen therapy regimen. |
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Heritage Products Hydrogen Peroxide Mouthwash, 16-Ounces (Pack of 4) by Heritage Store Unique foaming action. Oxygenating formula. Wakes up your mouth. Refreshing taste. Seal of approval not tested on animals. |
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FOOD GRADE H2O2 - 8% by Family Health FOOD GRADE 8% Hydrogen Peroxide solution is good for disinfecting water, a foliar spray, chemical free cleaning and bleaching. 1 Pint - 16 oz. |
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Hydrogen Peroxide: Medical Miracle by William Campbell Douglass II (Author) Peroxides are supposed to be bad for you. Free radicals and all that. But now we hear that hydrogen peroxide is good for us. Hydrogen peroxide will put extra oxygen in your blood. There's no doubt about that. Hydrogen peroxide costs pennies. So if you can get oxygen into the blood cheaply and safely, maybe cancer (which doesn't like oxygen), emphysema, AIDS, and many other terrible diseases can be treated effectively. Intravenous hydrogen peroxide rapidly relieves allergic reactions, influenza symptoms, and acute viral infections. No one expects to live forever. But we would all like to have a George Burns finish. The prospect of finishing life in a nursing home after abandoning your tricycle in the mobile home park is not appealing. Then comes the loss of control of vital functions the... |
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HYDROGEN PEROXIDE ANTISEPTIC SOLUTION GALLON by VI-JON/CUMBERLAND SWAN First Aid Antiseptic, oral debriding agent. For treatment of minor cuts and abrasions or for use as a gargle or mouth rinse. Helps prevent the risk of infection in cuts, scrapes and burns. Aids in the removal of phlegm, mucus or other secretions associated with occassional sore mouth. Contains 3% hydrogen peroxide. 1 gallon bottle. |
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Hydrogen Peroxide --- 32 Oz by PREFFERED PLUS PRODUCTS SKU NUMBER: 509174The Mininimum EXP date on product:1Year.TITLE DESCRIPTION: Hydrogen Peroxide --- 32 OzMANUFACTURER:PREFFERED PLUS PRODUCTS. PRODUCT DESCRIPTION:Hydrogen Peroxide, 3%. Local antiseptic commonly used for minor cuts and abrasions. |
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O-W & Company - H2O2 Hydrogen Peroxide (Contains 12% Aqueous Solution Food Grade H2O2) 16 fl. oz. by O-W & Company |
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Hydrogen Peroxide: Medical Miracle by William Campbell Douglass (Author) Peroxides are supposed to be bad for you. Free radicals and all that. But now we hear that hydrogen peroxide is good for us. Hydrogen peroxide will put extra oxygen in your blood. There's no doubt about that. Hydrogen peroxide costs pennies. So if you can get oxygen into the blood cheaply and safely, maybe cancer (which doesn't like oxygen), emphysema, AIDS, and many other terrible diseases can be treated effectively. Intravenous hydrogen peroxide rapidly relieves allergic reactions, influenza symptoms, and acute viral infections. No one expects to live forever. But we would all like to have a George Burns finish. The prospect of finishing life in a nursing home after abandoning your tricycle in the mobile home park is not appealing. Then comes the loss of control of... |
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CASE 8% FOOD GRADE - 9 PINTS by Family Health FOOD GRADE 8% Hydrogen Peroxide. Buy the case nine pints of eight percent good grade. Hot tubs, bathing & sprouting |
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