hu wissen (pdf) - Exzellenzinitiative - Humboldt-Universität zu Berlin

Mäuse, die das Cystatin verabreicht
bekommen, entwickeln
kein allergisches Asthma und
weder Hautallergien noch
Darmentzündungen
Experiments using animals have
shown that when the cystatin is
administered to mice, they develop
neither allergic asthma, nor skin
allergies, nor enteritis
blood cell. These get to work together and kill the worm parasites.
During the battle they call legions of other immune cells to the site
of the action. The tissue becomes infl amed. Richard Lucius and
Susanne Hartmann, who work at the Department of Biology, have
now discovered how the cystatin puts the brake on the immune
system: »The protein infl uences macrophages. These are important
scavenger and defence cells, part of the immune system,« explains
Ms Hartmann, who is head of the working group on helminths.
»The macrophages change their metabolism and their cell surface,
among other things. They also give off substances that suppress
other immune cells.« Various studies show that patients who are
infected by a large number of microfi lariae have infl ammations
relatively rarely, an indication that the worms slow down the infl
ammatory immune responses in order not to be killed off by
them. »Parasitic worms are able to infl uence immune responses in
a very targeted way,« says Ms Hartmann. »They are great immunologists!«
The HU biologists have isolated the gene that is responsible
for producing cystatin from the worm and inserted it into bacteria,
thus making them produce the protein. The experts call this a
recombinant, i.e. genetically manufactured protein. Experiments
using animals have shown that when the cystatin is administered
to mice, they develop neither allergic asthma, nor skin allergies,
nor enteritis (intestinal infl ammation). »Allergies and certain
forms of infl ammation are actually anti-worm responses, and
these are inhibited by the protein,« says Lucius. The American gastroenterologist
Prof. Joel Weinstock of Tu� s University in Boston
has already made use of this fi nding in an experiment. He administered
pig whipworm eggs to patients suff ering from chronic enteritis.
The roundworms that hatch from the eggs are adapted to
pigs. In a human intestine they release their immunomodulating
196
agents, but die shortly a� erwards. In two clinical studies Weinstock
was able to show that the patients’ symptoms improved signifi
cantly, and were even cured a� er repeated treatment. »The
worm eggs have not yet been approved as a drug in Germany,«
says Richard Lucius, »but clinical trials on the eff ect of this treatment
are in progress.«
The parasitologist is collaborating closely with pharmaceutical
companies. Together, the scientists are trying to get to the bottom
of cystatin’s exact mechanism of action. »We want to examine
which part of the cystatin molecule stimulates the surface receptors
of macrophages so that we can imitate the protein one day
with a corresponding substance.«
In a project that is scheduled for four and a half years and
funded by the German Research Foundation, the molecular parasitology
team are investigating the protein’s mode of action in
people infected with Wuchereria. This is the name of a roundworm
that lives in lymph vessels and is transmitted by mosquitoes.
Some 120 million people are aff ected by it worldwide. Together
with scientists from the University of Hyderabad, the capital of the
Indian state of Andhra Pradesh, they are examining inhabitants
of a village near that city, asking them about their symptoms,
which can vary greatly, taking blood samples and examining the
blood cells right down to the genes. »This enables us to study the
genetic bases of the immune response and to fi nd out how it is
aff ected by the worm protein.« The big question will be whether
they can outwit Wuchereria …
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