Antibody ‘Fixes Internal Bleeds’

Scientists say they have discovered an antibody that could minimise the major internal bleeding seen in traumas like bullet wounds and car crashes.
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The team at Oklahoma Medical Research Foundation (OMRF) has discovered that a protein called histone is responsible for much of the damage.

They say they have found a specific type of antibody that can block the ability of histone to cause damage.

They say it could lead to new ways to treat diseases and serious injuries.

‘Life threatening’
Writing in the journal, Nature Medicine, the OMRF researchers found that when mice had a bad blood stream infection (sepsis), their blood contained high levels of histones.

They checked this in primates and humans and found the same result.

The histone protein normally sits in the nucleus of a cell, packed around the strands of DNA.

It regulates the DNA, causing it to fold and form the characteristic double helix.


Bullet wounds often lead to severe internal bleeding

When the cell is damaged by injury or disease, the histone is released into the blood system where it begins to kill the lining of blood vessels, causing damage, the OMRF researchers said.

This, they believe, results in uncontrolled internal bleeding and fluid build-up in the tissues, which are life threatening.

Dr Charles Esmon, of OMRF who led the research, said: “When we realised that histones were so toxic, we immediately went to work looking for a way to stop their destructive tendencies.”

Mouse antibody
Marc Monestier, a colleague at Temple University in Philadelphia, had already discovered a specific type of antibody known as a monoclonal antibody that could block the histones.

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It had been observed that patients with auto-immune diseases make antibodies to the proteins in their cell nuclei but it was not known why.

This antibody came from a mouse with an auto-immune disease.

The OMRF team have tested the antibody in mice with sepsis and it does stop the toxic effects of the histones and they recover, the researchers say.

They now want to test it in primates and eventually humans.

Dr Esmon said histones were similar in all mammals because they were such basic building blocks.

So a mouse antibody should work equally well in a human.

He said: “We think it was an adaptation during evolution.

“Millions of years ago, when people and animals got ill, they did not die of heart attacks or car accidents they died of infectious diseases.

“Their immune systems went into overdrive throwing everything at it and we believe the histones in the cell nucleus, part of the basic building blocks of life, were the last resort.”

Dr Stephen Prescott, president of OMRF, said: “These findings offer some clues as to why people suffering from one traumatic injury often experience a catastrophic ‘cascade’ of secondary traumatic events.

“If we can figure out how to control the initial injury, perhaps that will stop the domino effect that so often follows.”

Source: BBC News: 26th.Oct.’09

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