A medication that can protect people exposed
to normally lethal doses of radiation from a nuclear or a
"dirty" bomb has been developed, reports say.
In tests involving 650 monkeys exposed to radiation equivalent
to that recorded during the Chernobyl nuclear reactor disaster
in 1986, 70 per cent died while the rest suffered serious
maladies, the newspaper Yediot
Achronot said yesterday.
Of the group given anti-radiation shots, almost all survived
and had no side effects. A test on humans not exposed to
radiation showed none suffered side effects from the
medication.
The medication was developed by Andrei Gudkov, chief
scientific officer at Cleveland BioLabs in the US. Also
involved was Israel's Elena Feinstein.
"We made a breakthrough that may save the lives of millions,"
Dr Gudkov was quoted as saying.
The medication has important implications in the treatment of
cancer, the report said, since it permits use of more powerful
radiation.
If the medication is given final approval by the Food and Drug
Administration, which Dr Gudkov said would happen within two
years, it could have a strategic impact, particularly for
nations threatened with nuclear attack. Among the major fears
in the West is not nuclear attack but "dirty bombs", which
kill mostly by radiation.
Dr Gudkov conceived the idea in 2003 of using protein produced
in bacteria found in the intestine to protect cells from
radiation. "The medication works by suppressing the 'suicide
mechanism' of cells hit by radiation," the newspaper said,
"while enabling them to recover from the radiation-induced
damages that prompted them to activate the suicide mechanism
in the first place."
The medication is a preventative drug administered by one or
several doses.
Flagellin
Flagellin is a protein that arranges itself in a hollow
cylinder to form the filament in bacterial flagellum. It has a
mass of about 30,000 to 60,000 daltons. Flagellin is the
principal substituent of bacterial flagellum, and is present
in large amounts on nearly all flagellated bacteria.
Structure
The structure of flagellin is responsible for the helical
shape of the flagellar filament, which is important for its
proper function.
The N- and C-termini of flagellin form the inner core of the
flagellin protein, and is responsible for flagellin's ability
to polymerize into a filament. The central portion of the
protein makes up the outer surface of the flagellar filament.
While the termini of the protein is quite similar between all
bacterial flagellins, the central portion is wildly variable.
Immune response
In mammals
Mammals often have acquired immune responses (T-cell and
antibody responses) to flagellated bacterium occurs frequently
to flagellar antigens. Some bacteria are able to switch
between multiple flagellin genes in order to evade this
response.
The propensity of the immune response to flagellin may be
explained by two facts:
First, flagellin is an extremely abundant protein in
flagellated bacteria.
Secondly, there exists a specific innate immune receptor that
recognizes flagellin, Toll-like receptor 5 (TLR5).
In plants
In addition a 22 amino acid sequence (flg22) of the conserved
N-terminal part of flagellin is known to activate plant
defence mechanisms. Flagellin perception in Arabidopsis
thaliana functions via the receptor-like-kinase, FLS2
(flagellin-sensitive-2)). Mitogen-activated-protein-kinases
(MAPK) acts as signalling compounds and more than 900 genes
are affected upon flg22 treatment.
Pre-stimulation with a synthetic flg22-peptide led to enhanced
resistance against bacterial invaders.
http://www.nlm.nih.gov/cgi/mesh/2009/MB_cgi?mode=&term=Flagellin\
MeSH Heading -- Flagellin
Tree Number -- D12.776.097.380
Annotation - a bact protein
Scope Note -- A protein with a molecular weight of
40,000 isolated from bacterial flagella. At appropriate pH and
salt concentration, three flagellin monomers can spontaneously
reaggregate to form structures which appear identical to
intact flagella.
Bacterial flagellin activates
basolaterally expressed TLR5 to induce epithelial
proinflammatory gene expression.
Gewirtz AT, Navas TA, Lyons
S, Godowski PJ, Madara JL.
Epithelial Pathobiology Division, Department of Pathology and
Laboratory Medicine, Emory University, Atlanta, GA 30322, USA
ski@gene.com.
Flagellin, the structural component of bacterial flagella, is
secreted by pathogenic and commensal bacteria. Flagellin
activates proinflammatory gene expression in intestinal
epithelia. However, only flagellin that contacts basolateral
epithelial surfaces is proinflammatory; apical flagellin has
no effect. Pathogenic Salmonella, but not commensal
Escherichia coli, translocate flagellin across epithelia, thus
activating epithelial proinflammatory gene expression.
Investigating how epithelia detect flagellin revealed that
cell surface expression of Toll-like receptor 5 (TLR5)
conferred NF-kappaB gene expression in response to flagellin.
The response depended on both extracellular leucine-rich
repeats and intracellular Toll/IL-1R homology region of TLR5
as well as the adaptor protein MyD88. Furthermore,
immunolocalization and cell surface-selective biotinylation
revealed that TLR5 is expressed exclusively on the basolateral
surface of intestinal epithelia, thus providing a molecular
basis for the polarity of this innate immune response. Thus,
detection of flagellin by basolateral TLR5 mediates
epithelial-driven inflammatory responses to Salmonella.
WO2005056042
METHODS OF PROTECTING AGAINST
RADIATION USING FLAGELLIN
Abstract --The
invention relates to a method of protecting a mammal against
radiation comprising administering said mammal a composition
containing flagellin.
Also published as: WO2005056042 // WO2005056055
// WO2005056055 // WO2005057218
