Mice smoke out key emphysema gene
 (From Science News, volume 152 #13, 9/27/97.  Author:  John Travis.
 Reproduced without permission.  Typos are mine.)
 
With every breath of life-giving air, elastic fibers in the lungs help
those organs expand and contract.  For the 2 million people suffering
from emphysema, a disease usually induced by smoking, this essential
routine doesn't come easily.
 
From a variety of evidence, emphysema investigators have theorized
that the destruction typical of this disease results when large
numbers of immune cells migrate to the lungs and release enzymes that
degrade elastin, the major protein in the elastic fibers there.
 
Now, by creating mice that lack one such enzyme and showing that they
resist smoke-induced emphysema, scientists have garnered strong
support for this explanation of the disease.
 
"The hypothesis has lasted 30 years, and now we're able, with modern
genetic manipulation, to confirm it directly in mammals," says Steven
D. Shapiro of Washington University School of Medicine's Barnes-Jewish
Hospital in St. Louis.
 
The results, also reported in the Sept. 26 SCIENCE, also add a subtle
twist to the odd hypothesis.  They highlight different immune cells,
ones called macrophages, from those on which emphysema researchers had
previously focused their studies.
 
Shapiro's experiments on the genetically engineered mice are "the
first to suggest in an animal model that the presence of macrophages
is esential to the development of smoke-induced emphysema," says
Gordon L. Snider of the Boston Veterans Affairs Medical Center, who
has studied the disease for decades.
 
Shapiro and his colleagues verified that they could induce emphysema
in mice by placing the animals in a smoking chamber where the rodents
were exposed to the equivalent of two nonfiltered cigarettes a day, 6
days a week, for up to 6 months.
 
When the scientists examined the lungs of the animals, they found all
the characteristic signs of emphysema.  "Early on, there's a
recruitment of inflammatory cells, predominantly macrophages, and
that's followed by a gradual destruction [of lung tissue] and
enlargement of the air spaces," says Shapiro.
 
The researchers then used the smoking chamber to test mice genetically
engineered to lack the macrophage enzyme called MME.  This enzyme
breaks down several proteins, including elastin.  The mutant mice did
not suffer the lung destruction observed in unaltered mice.
 
Another finding surprised Shapiro and his colleagues.  They had
assumed that the macrophages lacking MME still rushed into the lungs.
The scientists found few immune cells in the lungs of the mutant mice,
however.
 
To explain the absence of macrophages, Shapiro suggests that cigarette
smoke signals the few immune cells normally patrolling the lungs to
release MME.  This enzyme, in addition to destroying elastin, somehow
attracts more macrophages.  Consequently, macrophages without MME do
not recruit additional immune cells to the lungs.
 
Until recently, most research on emphysema centered on elastin-destroying
enzymes made by immune cells called neutrophils, even though
macrophages make up 90 percent of immune cells in the lungs, notes
Snider.
 
Compounds that inhibit enzymes similar to MME and the neutrophil
enzymes are under development to treat cancer and may be adapted for
the treatment of emphysema, adds Shapiro.  He speculates that
cigarette makers may one day add such protective compounds to their
product.

2 responses total.

What health effects result from the suppression of MME? I would think
that the enzyme exists because of some useful role in other lung
infections. Would suppressing MME make the symptoms of, say viral
pneumonia much worse, or even more likely fatal?

That's an excellent question, which the research detailed above was
obviously not set up to answer.

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