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 Drone vs. truck deliveries: Which create less carbon pollution?
31.05.2017 | University of Washington

nachricht New study: How does Europe become a leading player for software and IT services?
03.04.2017 | Fraunhofer-Institut für System- und Innovationsforschung (ISI)

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: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Touch Displays WAY-AX and WAY-DX by WayCon

27.06.2017 | Power and Electrical Engineering

Drones that drive

27.06.2017 | Information Technology

Ultra-compact phase modulators based on graphene plasmons

27.06.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>