This might explain some of the neuronal cascade of death. So whom is working on this?
http://www.alphagalileo.org/ViewItem.aspx?ItemId=143009&CultureCode=en
Even after a cell dies, components of the immune system remain active
and continue to fuel inflammatory reactions. An international team of
researchers under the direction of scientists from the Institute of
Innate Immunity at the University Hospital of Bonn has discovered how
this incredible form of communication works. The findings offer
potentially novel approaches for therapies against many serious diseases
that affect a large part of the population, such as gout,
atherosclerosis and Alzheimer's disease. The exciting new results are
now published in the renowned journal "Nature Immunology".
When there is stress in living immune cells, – for example due to the
detection of microbes, or the deposition of uric acid crystals in
joints, cholesterol in blood vessels or Alzheimer's plaques in the brain
– the so-called ‘inflammasome’ sounds the alarm. Inflammasomes are
large multiprotein complexes, which form when they sense cell stress.
The inflammasomes activate an enzyme, which stimulates important
messengers that in turn trigger an inflammatory reaction. During this
cell activation, the affected immune cells die and thus the inflammatory
reaction should come to a halt. "This mechanism primarily protects the
body from infections and harmful influences," says Prof. Eicke Latz, the
director of the Institute of Innate Immunity at the University Hospital
in Bonn.
Strikingly, these new findings reveal that inflammasomes remain
active even when the cells have died. The scientists were able to
demonstrate that activated inflammasomes also have enzymatic functions
outside of the living cell and can thus activate additional messengers.
In a type of chain reaction, the inflammasomes released from dying cells
are taken up by neighboring immune cells where they can activate more
inflammasomes. This discovery was made by an international team of
researchers under the direction of the members from the Institute of
Innate Immunity, together with scientists from Hannover Medical School,
the University of Massachusetts Medical School (USA), the German Center
for Neurodegenerative Diseases (DZNE) in Bonn, the University of
Trondheim (Norway), the University of Newcastle (Australia) and the
Zurich University Hospital (Switzerland).
Protein complexes shift into defense mode
When the inflammasomes are switched on, within seconds they form
functional protein complexes, which can be as large as a bacterium. "In
the event of stress or infection, this protein complex forms and
provokes the activation of pro-inflammatory messengers within the cell
and – as we now know – this can also occur outside of the cell. In this
way, there can be a very rapid inflammatory reaction which helps the
undesired insult or microbial invaders to be eliminated as quickly as
possible," explains lead author Dr. Bernardo S. Franklin, a fellow of
the Alexander von Humboldt Foundation working in Prof. Latz's team.
Using fluorescence techniques, the researchers labeled the
inflammasome in immune cells. Whenever it was active, it formed a
fluorescent protein complex, reminiscent of small stars glowing inside
the cell. Using this method, the scientists were able to track the
inflammasome after cell death, and show that it remained switched on as
an intact protein complex. They also found that once released from the
dead cell, it stimulated neighboring cells to undergo an inflammatory
reaction. Furthermore, they found that these extracellular complexes
accumulate in the lungs of patients with chronic lung disease.
Starting points for new therapies against widespread diseases
"Normally, the immune system is very helpful for averting harmful
damage to tissue by initiating an inflammatory reaction," says Prof.
Latz. However, if such inflammatory reactions are excessive or if they
persist for longer than necessary, this may contribute to common
diseases of Western society, such as gout, Alzheimer's disease, diabetes
or atherosclerosis. With the discovery of extracellular inflammasomes,
the researchers have revealed an interesting avenue for potential new
therapies: "If we are able to produce suitable antibodies, it is likely
we could contain the alarm of the inflammasome outside of cells and thus
keep harmful chronic inflammatory reactions at bay, without affecting
the necessary response inside the cell" says Prof. Latz.
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