Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Stanford snake venom study shows that certain cells may eliminate poison

31.07.2006
Death by snakebite is horrible. The immediate pain of the bite is followed by swelling, bruising and weakness, then sweating or chills, with numbness, nausea, blurred vision and possibly convulsions before it's all over. Such misery is produced by a veritable witches' brew of toxins in snake venom.

It's long been thought that the body's own immune system, rather than reducing the symptoms, may make things worse. But now researchers at the Stanford University School of Medicine have shown that the immune system really does side with the victim, at least in four kinds of venom that were used in their experiments. Their findings will be published in the July 28 issue of Science.

Venom from three species of poisonous snakes and one species of honeybee were studied by a group led by Stephen Galli, MD, professor and chair of the Department of Pathology. Using mice, they analyzed how mast cells, a vital part of the immune system in mammals, reacted to the various venoms. The net effect of the mast cell response to the four venoms "is to enhance resistance to the toxicity and reduce mortality induced by the venom," said Galli, the paper's senior author.

This helpful mast cell response runs contrary to the conventional wisdom - that the immune system only added to the woes of snakebite victims. This assumption arose because of the way mast cells respond to certain other stimuli.

Mast cells synthesize a wide range of biological mediators - compounds that can promote inflammation and other tissue changes - that are selectively unleashed from the cells in response to various triggers, often intruders such as parasites or bacteria. In people who have been sensitized (i.e., made allergic) by prior exposure to substances such as peanuts or certain pollens, mast cells also respond to those stimuli. When mast cells overreact to allergens, they contribute to the effects associated with allergy attacks, such as a runny nose, sneezing, itching and red eyes. When they severely overreact, they can cause anaphylaxis, which can be fatal.

Given that tendency to overreact when stimulated by allergens, it seemed plausible that introducing venom into the body would trigger a similar response. But Galli and Martin Metz, MD, a postdoctoral scholar in pathology and first author of the study, have shown that when mast cells respond to selected venoms, they unleash proteins that break down some of the venoms' most toxic components.

The study was inspired by a 2004 paper in Nature, by Galli and a team of researchers including Metz, showing that mast cells reduced the mortality rate of mice suffering from bacterial peritonitis, a severe bacterial infection in the abdominal cavity that can also be fatal to humans. They found that mast cells released proteins that broke down a molecule called endothelin-1, one of the major toxins produced by the body during bacterial peritonitis or sepsis (bacterial infection in the blood).

In perusing the scientific literature, Metz noticed that endothelin-1 bore a striking similarity to sarafotoxin 6b, the most toxic component in the venom of the burrowing asp, or Israeli mole viper. Knowing also that mammalian mast cells had been shown to respond to many snake venoms by secreting some potent biologically active mediators, they hypothesized that mast cells might also act to degrade sarafotoxins and reduce the toxicity of the Israeli mole viper venom.

Galli and Metz first did experiments in vitro using isolated sarafotoxin 6b with mast cells from mice. "It worked as we thought it would," said Metz. The mast cells were activated, they released the expected proteins and the proteins degraded the sarafotoxin 6b. Mast cells also enhanced resistance of mice to sarafotoxin 6b when it was injected in vivo.

Next, Galli and Metz did experiments using the whole venom, not just the isolated toxin. Some of the mice they worked with were genetically deficient in mast cells, while others, called wild-type mice, had normal mast cells. "We saw the same results in the wild-type mice that we saw before with just the one component, sarafotoxin 6b," said Metz. The mast cells were activated via a particular receptor they had on the cell surface and released the appropriate proteins, which, Metz said, went on to "degrade and thus eliminate the venom, or at least make it less toxic."

The wild-type mice were able to withstand 10 times the dosage of this venom than the mast cell deficient mice could, further indicating that the mast cells were reducing the impact of the venom. To test whether mast cells could also reduce the toxicity of venom from snakes that didn't contain toxins comparable to sarafotoxin 6b, Galli and Metz tested the venom of the western diamondback rattlesnake and the southern copperhead. Again, the mast cells conferred a distinct protective edge.

Testing the mast cell response even further, they also experimented with the venom from honeybees, with the same positive result. "The mast cells significantly limit not only the toxicity, but also the mortality associated with the venom," said Galli.

But Galli called the battle between predators with venom and their prey "a kind of evolutionary arms race." He and Metz suspect that, given the broad range of venoms that have been developed by snakes and other creatures, mast cells probably won't perform as well against every type of venom.

"We expect that there will be some snake venoms that either are not affected by mast cells at all or perhaps even elicit more pathology due to their ability to activate mast cells. It all depends on the balance between the positive and negative effects of the mediators released by mast cells in response to a particular venom," said Galli.

Galli and Metz are embarking on a systematic survey of animal venoms. As more is learned about the natural defenses the mammalian immune system has against venom, it may someday even lead to better antivenins, though it will first have to be shown that human mast cells respond in the same way mouse mast cells do. The group has begun in vitro studies using human mast cells to evaluate this possibility.

Louis Bergeron | EurekAlert!
Further information:
http://www.stanford.edu

More articles from Studies and Analyses:

nachricht Smart Data Transformation – Surfing the Big Wave
02.12.2016 | Fraunhofer-Institut für Angewandte Informationstechnik FIT

nachricht Climate change could outpace EPA Lake Champlain protections
18.11.2016 | University of Vermont

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Simple processing technique could cut cost of organic PV and wearable electronics

06.12.2016 | Materials Sciences

3-D printed kidney phantoms aid nuclear medicine dosing calibration

06.12.2016 | Medical Engineering

Robot on demand: Mobile machining of aircraft components with high precision

06.12.2016 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>