by reducing the immune reaction.
However, serine protease activity comes at a cost. The enzymes not only heal inflammations, but sometimes cause them in the first place. If too many immune cells are activated, they can use their arsenal of aggressive chemical weapons against the body's own tissues. A number of chronic inflammatory diseases are based on precisely this effect. As a result, scientists are searching for substances that can block the neutrophil proteases. To date, however, none of the substances tested have been developed into effective drugs.
"So far, we don't know the identity of the NSP4 substrate, but we assume they must be signal molecules", says Dieter Jenne. Activated chemokines can recruit a vast number of neutrophils, and their sheer quantity alone is enough to cause tissue damage. "Proteases sometimes act as accelerants and can even trigger a chronic inflammation quite independently of bacterial intruders. If we dampened down the defences, we could counteract this effect", explains the scientist.
In terms of evolutionary history, NSP4 is the oldest of the four known neutrophil serine proteases. Using gene sequences, scientists have shown that the enzyme has hardly changed through hundreds of millions of years of evolution from bony fish to humans. "That would indicate that NSP4 regulates a fundamental process", says Dieter Jenne.
The fact that the enzyme remained undiscovered until now is because it occurs at a much lower concentration than the other three proteases. The Max Planck scientists came across it while searching the human genome for genes that encode serine proteases. In the process, they noticed a previously unknown gene sequence. Natascha C. Perera, a member of the Martinsried research group and lead author of the study, managed to produce and examine the enzyme in its active, folded state.
If they are to establish NSP4 in the future as a possible target protein for anti-inflammatory dru
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| Contact: Dr. Dieter Jenne djenne@neuro.mpg.de 49-898-578-3588 Max-Planck-Gesellschaft Source:Eurekalert |
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