Bleeding, not inflammation, is major cause of early lung infec... (lockage of blood flow or a protective me...)

Bleeding, not inflammation, is major cause of early lung infection death

Date:8/27/2007

lockage of blood flow, or a protective mechanism that prevents unchecked bleeding, all depending on a careful balance.

Specifically, the ability of blood to clot is increased by one regulatory pathway of reactions that end with the activation of a protein called plasminogen activator 1 (PAI-1). Against the pro-clotting influence of PAI-1 is balanced the action of another protein, cylindromatosis (CYLD), which blocks the clotting pathway just enough to keep blood flowing under normal circumstances. What Li and colleagues found is that the S. pneumoniae bacteria release a protein called pneumolysin, which causes an overproduction of CYLD, which increases the permeability of the lungs blood vessels and causes them to leak blood. They also found that pneumolysin directly increases the permeability of the lungs blood vessels, which causes yet more bleeding. Furthermore, antibiotic drugs kill bacteria by cutting them open, which releases of even more pneumolysin.

Lis team found for the first time that too much CYLD inhibits a signaling molecule (p38 kinase), which leads to reduced expression of PAI-1 expression in lung. To prove the point further, Lis team genetically engineered mice that do not have CYLD, and found that very few die of S. pnuemoniae infection.

The most immediate implication of this work is that we could make purified, recombinant PAI-1 and inject it directly into the lungs of these patients, and it would have a benefit, Li said. The next step will be to design a small molecule, a protein fragment, that can mimic PAI-1, which would be easier to deliver in the lungs, more effective and have fewer side effects. It would be even better if we could design an aerosol form, so you could just spray it into the air around these patients and their bleeding would stop.

Contact: Greg Williams
Greg_Williams@urmc.rochester.edu
University of Rochester Medical Center
Source:Eurekalert

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GOOD

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Bleeding, not inflammation, is major cause of early lung infec...(lockage of blood flow or a protective me...)